MUTYH p.Ser543Phe

Variant names:

• chr1-45329265-CT-AA
• NM_001128425.2:c.*40_*41delAGinsTT

Your query was ambiguous. Multiple possible variants found:

• chr1-45329265-CT-AA
• chr1-45329319-CT-AA
• chr1-45329328-CT-AA
• chr1-45329264-ACT-GAA
• chr1-45329318-ACT-GAA
• chr1-45329327-GCT-AAA

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_001407087.1(MUTYH):c.*40_*41delAGinsTT variant causes a 3 prime UTR change. Note: NM_001407087.1 is not a MANE Select or MANE Plus Clinical transcript for MUTYH; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MUTYH NM_001407087.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MUTYH Gene-Disease associations (from GenCC):

• familial adenomatous polyposis 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• colorectal cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: AR, AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000288208 (HGNC:):

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.0005 by highest known P/LP ClinVar AF 0.00473) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001407087.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MUTYH NM_001128425.2	MANE Plus Clinical	c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001121897.1 UniProt:
	MUTYH NM_001048174.2	MANE Select	c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001041639.1 UniProt:
	MUTYH NM_012222.3		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_036354.1 UniProt:
	MUTYH NM_001293190.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001280119.1 UniProt:
	MUTYH NM_001407083.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394012.1 UniProt:
	MUTYH NM_001407085.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394014.1 UniProt:
	MUTYH NM_001293191.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001280120.1 UniProt:
	MUTYH NM_001407069.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001393998.1
	MUTYH NM_001407077.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394006.1 UniProt:
	MUTYH NM_001407087.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 17 of 17	Prot: NP_001394016.1 UniProt:
	MUTYH NM_001048172.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001041637.1 UniProt:
	MUTYH NM_001407071.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394000.1 UniProt:
	MUTYH NM_001407078.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 17 of 17	Prot: NP_001394007.1 UniProt:
	MUTYH NM_001407086.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394015.1 UniProt:
	MUTYH NM_001048171.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001041636.2 UniProt:
	MUTYH NM_001048173.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001041638.1 UniProt:
	MUTYH NM_001293195.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 17 of 17	Prot: NP_001280124.1 UniProt:
	MUTYH NM_001407070.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001393999.1 UniProt:
	MUTYH NM_001407072.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394001.1 UniProt:
	MUTYH NM_001407073.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001394002.1
	MUTYH NM_001407081.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 17 of 17	Prot: NP_001394010.1 UniProt:
	MUTYH NM_001407088.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 17 of 17	Prot: NP_001394017.1 UniProt:
	MUTYH NM_001407089.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394018.1 UniProt:
	MUTYH NM_001407079.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001394008.1
	MUTYH NM_001407080.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001394009.1
	MUTYH NM_001407075.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394004.1
	MUTYH NM_001293192.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001280121.1
	MUTYH NM_001293196.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001280125.1
	MUTYH NM_001407091.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: NP_001394020.1
	MUTYH NM_001350650.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001337579.1
	MUTYH NM_001350651.2		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001337580.1
	MUTYH NM_001407082.1		c.*40_*41delAGinsTT	3_prime_UTR	Exon 15 of 15	Prot: NP_001394011.1
	MUTYH NR_146882.2		n.2014_2015delAGinsTT	non_coding_transcript_exon	Exon 17 of 17	Prot:
	MUTYH NR_146883.2		n.1863_1864delAGinsTT	non_coding_transcript_exon	Exon 16 of 16	Prot:
	MUTYH NR_176269.1		n.2010_2011delAGinsTT	non_coding_transcript_exon	Exon 17 of 17	Prot:
	MUTYH NR_176271.1		n.1873_1874delAGinsTT	non_coding_transcript_exon	Exon 17 of 17	Prot:
	MUTYH NR_176272.1		n.1937_1938delAGinsTT	non_coding_transcript_exon	Exon 17 of 17	Prot:
	MUTYH NR_176273.1		n.1895_1896delAGinsTT	non_coding_transcript_exon	Exon 16 of 16	Prot:
	MUTYH NR_176274.1		n.1950_1951delAGinsTT	non_coding_transcript_exon	Exon 17 of 17	Prot:

MUTYH NM_001128425.2

MANE Plus Clinical

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001121897.1UniProt: E5KP25

MUTYH NM_001048174.2

MANE Select

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001041639.1UniProt: Q9UIF7-6

MUTYH NM_012222.3

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_036354.1UniProt: Q9UIF7-1E5KP26

MUTYH NM_001293190.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001280119.1UniProt: Q9UIF7-2

MUTYH NM_001407083.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394012.1UniProt: E9PM53

MUTYH NM_001407085.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394014.1UniProt: E9PM53

MUTYH NM_001293191.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001280120.1UniProt: Q9UIF7-4

MUTYH NM_001407069.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001393998.1

MUTYH NM_001407077.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394006.1UniProt: Q9UIF7-4

MUTYH NM_001407087.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 17 of 17

3_prime_UTR

Prot: NP_001394016.1UniProt: A0AAQ5BGW7

MUTYH NM_001048172.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001041637.1UniProt: E5KP28Q9UIF7-5

MUTYH NM_001407071.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394000.1UniProt: Q9UIF7-5E5KP28

MUTYH NM_001407078.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 17 of 17

3_prime_UTR

Prot: NP_001394007.1UniProt: Q9UIF7-5E5KP28

MUTYH NM_001407086.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394015.1UniProt: Q9UIF7-5E5KP28

MUTYH NM_001048171.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001041636.2UniProt: E5KP27Q9UIF7-6

MUTYH NM_001048173.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001041638.1UniProt: Q9UIF7-6

MUTYH NM_001293195.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 17 of 17

3_prime_UTR

Prot: NP_001280124.1UniProt: Q9UIF7-6

MUTYH NM_001407070.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001393999.1UniProt: Q9UIF7-6

MUTYH NM_001407072.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394001.1UniProt: Q9UIF7-6

MUTYH NM_001407073.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001394002.1

MUTYH NM_001407081.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 17 of 17

3_prime_UTR

Prot: NP_001394010.1UniProt: Q9UIF7-6

MUTYH NM_001407088.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 17 of 17

3_prime_UTR

Prot: NP_001394017.1UniProt: Q9UIF7-6

MUTYH NM_001407089.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394018.1UniProt: Q9UIF7-6

MUTYH NM_001407079.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001394008.1

MUTYH NM_001407080.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001394009.1

MUTYH NM_001407075.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394004.1

MUTYH NM_001293192.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001280121.1

MUTYH NM_001293196.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001280125.1

MUTYH NM_001407091.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: NP_001394020.1

MUTYH NM_001350650.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001337579.1

MUTYH NM_001350651.2

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001337580.1

MUTYH NM_001407082.1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 15 of 15

3_prime_UTR

Prot: NP_001394011.1

MUTYH NR_146882.2

HGVSc / HGVSpn.2014_2015delAGinsTT

Exon rankExon 17 of 17

non_coding_transcript_exon

Prot:

MUTYH NR_146883.2

HGVSc / HGVSpn.1863_1864delAGinsTT

Exon rankExon 16 of 16

non_coding_transcript_exon

Prot:

MUTYH NR_176269.1

HGVSc / HGVSpn.2010_2011delAGinsTT

Exon rankExon 17 of 17

non_coding_transcript_exon

Prot:

MUTYH NR_176271.1

HGVSc / HGVSpn.1873_1874delAGinsTT

Exon rankExon 17 of 17

non_coding_transcript_exon

Prot:

MUTYH NR_176272.1

HGVSc / HGVSpn.1937_1938delAGinsTT

Exon rankExon 17 of 17

non_coding_transcript_exon

Prot:

MUTYH NR_176273.1

HGVSc / HGVSpn.1895_1896delAGinsTT

Exon rankExon 16 of 16

non_coding_transcript_exon

Prot:

MUTYH NR_176274.1

HGVSc / HGVSpn.1950_1951delAGinsTT

Exon rankExon 17 of 17

non_coding_transcript_exon

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MUTYH ENST00000710952.2	MANE Plus Clinical	c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: ENSP00000518552.2 UniProt:
	MUTYH ENST00000456914.7	TSL:1MANE Select	c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: ENSP00000407590.2 UniProt:
	MUTYH ENST00000372098.7	TSL:1	c.*40_*41delAGinsTT	3_prime_UTR	Exon 16 of 16	Prot: ENSP00000361170.3 UniProt:

MUTYH ENST00000710952.2

MANE Plus Clinical

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: ENSP00000518552.2UniProt: E5KP25

MUTYH ENST00000456914.7

TSL:1MANE Select

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: ENSP00000407590.2UniProt: Q9UIF7-6

MUTYH ENST00000372098.7

TSL:1

HGVSc / HGVSpc.*40_*41delAGinsTT

Exon rankExon 16 of 16

3_prime_UTR

Prot: ENSP00000361170.3UniProt: Q9UIF7-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	1.6

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr1-45794937;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar