chr1-45331220-C-G

Position:

• chr1-45331220-C-G

Variant summary

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

The NM_001048174.2(MUTYH):​c.1354G>C​(p.Glu452Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E452V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MUTYH NM_001048174.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUTYH	NM_001048174.2	c.1354G>C	p.Glu452Gln	missense_variant	14/16	ENST00000456914.7	NP_001041639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7	c.1354G>C	p.Glu452Gln	missense_variant	14/16	1	NM_001048174.2	ENSP00000407590.2
ENSG00000288208	ENST00000671898.1	n.1942G>C		non_coding_transcript_exon_variant	18/21			ENSP00000499896.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;.;.;.;.;T;.;.;.;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	.;.;T;.;T;T;T;T;T;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	.;.;.;.;.;.;M;.;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;N;N;N;N;.
REVEL	Uncertain	0.49
Sift	Benign	0.038	D;T;T;T;T;T;T;T;T;D;T;.
Sift4G	Uncertain	0.015	D;T;T;T;T;T;T;T;T;D;T;T
Polyphen		0.014, 0.11, 0.065	.;.;.;.;.;.;B;B;.;.;B;.
Vest4		0.57
MutPred		0.61		.;.;.;.;.;.;.;.;.;.;Gain of MoRF binding (P = 0.0327);.;
MVP		0.97
MPC		0.17
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr1-45796892;