ENST00000475516.5:n.1416_1418delGTT

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6BS1BS2_Supporting

The ENST00000475516.5(MUTYH):n.*1416_*1418delGTT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,613,636 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 7 hom. )

Consequence

MUTYH
ENST00000475516.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.19

Publications

2 publications found

Variant links:

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: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
colorectal cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

MUTYH links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 1-45329266-TAAC-T is Benign according to our data. Variant chr1-45329266-TAAC-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 297466.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000571 (87/152242) while in subpopulation EAS AF = 0.0135 (70/5180). AF 95% confidence interval is 0.011. There are 0 homozygotes in GnomAd4. There are 57 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 7 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUTYH	NM_001048174.2 link	c.37_39delGTT		3_prime_UTR_variant	Exon 16 of 16	ENST00000456914.7	NP_001041639.1	Q9UIF7-6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000288208	ENST00000671898.1 link	n.346_348delGTT	non_coding_transcript_exon_variant	Exon 21 of 21			ENSP00000499896.1	A0A5F9ZGZ0
MUTYH	ENST00000456914.7 link	c.37_39delGTT	3_prime_UTR_variant	Exon 16 of 16	1	NM_001048174.2	ENSP00000407590.2	Q9UIF7-6
ENSG00000288208	ENST00000671898.1 link	n.346_348delGTT	3_prime_UTR_variant	Exon 21 of 21			ENSP00000499896.1	A0A5F9ZGZ0

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00107

AC:

269

AN:

251446

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000426

AC:

622

AN:

1461394

Hom.:

AF XY:

0.000437

AC XY:

318

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0110

AC:

437

AN:

39694

South Asian (SAS)

AF:

0.00133

AC:

115

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1111598

Other (OTH)

AF:

0.000613

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000571

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41534

American (AMR)

AF:

0.000131

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0135

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000808

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Familial adenomatous polyposis 2

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 20, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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ENST00000475516.5:n.1416_1418delGTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over