rs2228001

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM2_SupportingBP4_Strong

The NM_004628(XPC):c.2815C>G(p.Gln939Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 13/20 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. Q939K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

XPC
NM_004628 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.83

Links

XPC (HGNC:12816):

XPC-AS1 (HGNC:55014):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, Median coverage is 31.

BP4

Computational evidence support a benign effect (MetaRNN=0.04960659).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPC	NM_004628.5 linkuse as main transcript	c.2815C>G	p.Gln939Glu	missense_variant	16/16	ENST00000285021.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPC	ENST00000285021.12 linkuse as main transcript	c.2815C>G	p.Gln939Glu	missense_variant	16/16	1	NM_004628.5	P1	Q01831-1

Frequencies

GnomAD3 genomes

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Uncertain

0.97

DEOGEN2

Benign

0.046

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.78

M_CAP

Benign

0.0074

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.060

REVEL

Benign

0.12

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Polyphen

0.0

Vest4

0.069

MutPred

0.13

Loss of MoRF binding (P = 0.0837);

MVP

0.20

MPC

0.13

ClinPred

0.69

GERP RS

4.2

Varity_R

0.26

gMVP

0.073

Splicing

Find out SpliceAI 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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over