Variant rs3219467 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The ENST00000372098.7(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
ENST00000372098.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0940

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 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS2

High Homozygotes in GnomAdExome4 at 16 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/exons	MANE	Protein	UniProt
MUTYH	NM_001128425.2 linkuse as main transcript	c.36+75C>G		intron_variant		ENST00000710952.2	NP_001121897.1
TOE1	NM_025077.4 linkuse as main transcript			upstream_gene_variant		ENST00000372090.6	NP_079353.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000710952.2 linkuse as main transcript	c.36+75C>G		intron_variant			NM_001128425.2	ENSP00000518552
TOE1	ENST00000372090.6 linkuse as main transcript			upstream_gene_variant		1	NM_025077.4	ENSP00000361162	P1	Q96GM8-1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

331

AN:

152184

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00303

AC XY:

2149

AN XY:

710218

show subpopulations

Gnomad4 AFR exome

AF:

0.000337

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.000235

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.00395

Gnomad4 FIN exome

AF:

0.00226

Gnomad4 NFE exome

AF:

0.00335

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152302

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.00323

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000952

Hom.:

Bravo

AF:

0.00187

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

DANN

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over