3-14159826-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004628.5(XPC):​c.905T>C​(p.Phe302Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. F302V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

XPC
NM_004628.5 missense

Scores

8
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.10
Variant links:
Genes affected
XPC (HGNC:12816): (XPC complex subunit, DNA damage recognition and repair factor) The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
XPC-AS1 (HGNC:55014): (XPC antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XPCNM_004628.5 linkuse as main transcriptc.905T>C p.Phe302Ser missense_variant 8/16 ENST00000285021.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XPCENST00000285021.12 linkuse as main transcriptc.905T>C p.Phe302Ser missense_variant 8/161 NM_004628.5 P1Q01831-1
XPC-AS1ENST00000627116.2 linkuse as main transcriptn.457-6050A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.91
MutPred
0.65
Loss of stability (P = 0.0314);
MVP
0.50
MPC
0.74
ClinPred
1.0
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.88
gMVP
0.86

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.

Other links and lift over

dbSNP: rs121965091; hg19: chr3-14201326; API