rs75321043

Positions:

• chr1-45334474-C-A
• chr1-45334474-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001048174.2(MUTYH):​c.32G>T​(p.Gly11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G11D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MUTYH NM_001048174.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093682796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUTYH	NM_001128425.2	c.74G>T	p.Gly25Val	missense_variant	2/16	ENST00000710952.2
MUTYH	NM_001048174.2	c.32G>T	p.Gly11Val	missense_variant	2/16	ENST00000456914.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUTYH	ENST00000710952.2	c.74G>T	p.Gly25Val	missense_variant	2/16		NM_001128425.2
MUTYH	ENST00000456914.7	c.32G>T	p.Gly11Val	missense_variant	2/16	1	NM_001048174.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.24	N
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.094	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.20	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.15	N;N;N;N;N;N;N;N;N;N;N;D;N;N;N
REVEL	Benign	0.051
Sift	Benign	0.047	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;T;D;D;D;T;D;D;D;T;T;T;T;T
Polyphen		0.88, 0.93, 0.34	.;.;.;.;.;.;P;P;.;.;B;.;.;.;.
Vest4		0.25
MutPred		0.25		.;.;.;.;.;.;Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);.;Loss of relative solvent accessibility (P = 0.0071);.;.;.;.;
MVP		0.81
MPC		0.21
ClinPred		0.28	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45800146;