rs3176757

Variant names:

• chr9-97674776-G-A
• rs3176757
• XM_006717278.2:c.772+713C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_006717278.2(XPA):​c.772+713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 379,068 control chromosomes in the GnomAD database, including 8,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2745 hom., cov: 33)
  • Exomes 𝑓: 0.22 (6236 hom.)
• Consequence: XPA XM_006717278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPA	NM_000380.4	c.*663C>T		downstream_gene_variant		ENST00000375128.5	NP_000371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPA	ENST00000375128.5	c.*663C>T		downstream_gene_variant		1	NM_000380.4	ENSP00000364270.5
XPA	ENST00000462523.5	n.*921C>T		downstream_gene_variant		5		ENSP00000433006.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27061 AN: 152024 Hom.: 2747 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.220 AC: 49819 AN: 226926 Hom.: 6236 AF XY: 0.233 AC XY: 28539 AN XY: 122596

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.178 AC: 27061 AN: 152142 Hom.: 2745 Cov.: 33 AF XY: 0.183 AC XY: 13613 AN XY: 74336

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.179

Alfa AF: 0.191 Hom.: 4040

Bravo AF: 0.161

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.18
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3176757; hg19: chr9-100437058;