rs3219467

Variant names:

• chr1-45340144-G-C
• rs3219467
• NM_001128425.2:c.36+75C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-45340144-G-C
• chr1-45340144-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001128425.2(MUTYH):​c.36+75C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,584,652 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (16 hom.)
• Consequence: MUTYH NM_001128425.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 2 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]

ENSG00000288208 (HGNC:):

TOE1 (HGNC:15954): (target of EGR1, exonuclease) Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in RNA phosphodiester bond hydrolysis, exonucleolytic and snRNA 3'-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7. [provided by Alliance of Genome Resources, Apr 2022]

TOE1 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 7

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAdExome4 at 16 AR,AD geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128425.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUTYH	NM_001128425.2	MANE Plus Clinical	c.36+75C>G		intron	N/A	NP_001121897.1	E5KP25
	MUTYH	NM_012222.3		c.36+75C>G		intron	N/A	NP_036354.1	Q9UIF7-1
	MUTYH	NM_001293190.2		c.36+75C>G		intron	N/A	NP_001280119.1	Q9UIF7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUTYH	ENST00000710952.2	MANE Plus Clinical	c.36+75C>G		intron	N/A	ENSP00000518552.2	E5KP25
	MUTYH	ENST00000372098.7	TSL:1	c.36+75C>G		intron	N/A	ENSP00000361170.3	Q9UIF7-1
	MUTYH	ENST00000372110.7	TSL:1	c.36+75C>G		intron	N/A	ENSP00000361182.3	Q9UIF7-2

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 331 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00303 AC: 4334 AN: 1432350 Hom.: 16 Cov.: 33 AF XY: 0.00303 AC XY: 2149 AN XY: 710218

African (AFR) AF: 0.000337 AC: 11 AN: 32610

American (AMR) AF: 0.00102 AC: 41 AN: 40190

Ashkenazi Jewish (ASJ) AF: 0.000235 AC: 6 AN: 25566

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37586

South Asian (SAS) AF: 0.00395 AC: 324 AN: 82094

European-Finnish (FIN) AF: 0.00226 AC: 114 AN: 50500

Middle Eastern (MID) AF: 0.00371 AC: 20 AN: 5392

European-Non Finnish (NFE) AF: 0.00335 AC: 3678 AN: 1099174

Other (OTH) AF: 0.00235 AC: 139 AN: 59238

GnomAD4 genome AF: 0.00217 AC: 330 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00234 AC XY: 174 AN XY: 74478

African (AFR) AF: 0.000770 AC: 32 AN: 41556

American (AMR) AF: 0.00111 AC: 17 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4832

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00323 AC: 220 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000952 Hom.: 0

Bravo AF: 0.00187

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		-0.094
PromoterAI		-0.024	Neutral
Mutation Taster		=295/5	polymorphism

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

Other links and lift over

dbSNP: rs3219467; hg19: chr1-45805816; COSMIC: COSV104536723;