chr9-97675488-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000380.4(XPA):​c.773G>T​(p.Arg258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

XPA
NM_000380.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10
Variant links:
Genes affected
XPA (HGNC:12814): (XPA, DNA damage recognition and repair factor) This gene encodes a zinc finger protein plays a central role in nucleotide excision repair (NER), a specialized type of DNA repair. NER is responsible for repair of UV radiation-induced photoproducts and DNA adducts induced by chemical carcinogens and chemotherapeutic drugs. The encoded protein interacts with DNA and several NER proteins, acting as a scaffold to assemble the NER incision complex at sites of DNA damage. Mutations in this gene cause Xeroderma pigmentosum complementation group A (XP-A), an autosomal recessive skin disorder featuring hypersensitivity to sunlight and increased risk for skin cancer. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

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=0.23802474).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XPANM_000380.4 linkc.773G>T p.Arg258Leu missense_variant Exon 6 of 6 ENST00000375128.5 NP_000371.1 P23025

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XPAENST00000375128.5 linkc.773G>T p.Arg258Leu missense_variant Exon 6 of 6 1 NM_000380.4 ENSP00000364270.5 P23025
XPAENST00000462523.5 linkn.*209G>T non_coding_transcript_exon_variant Exon 7 of 7 5 ENSP00000433006.1 F2Z2T2
XPAENST00000485042.1 linkn.285G>T non_coding_transcript_exon_variant Exon 2 of 2 3
XPAENST00000462523.5 linkn.*209G>T 3_prime_UTR_variant Exon 7 of 7 5 ENSP00000433006.1 F2Z2T2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251144
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461542
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727054
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.013
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.90
L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.16
Sift
Benign
0.57
T
Sift4G
Benign
0.71
T
Polyphen
0.34
B
Vest4
0.34
MutPred
0.34
Loss of disorder (P = 0.0448);
MVP
0.78
MPC
0.34
ClinPred
0.40
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.39

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: rs763929562; hg19: chr9-100437770; API