rs3176649

Positions:

• chr9-97694251-TGTGC-T
• chr9-97694251-TGTGC-TGTGCGTGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000380.4(XPA):​c.173-496_173-493delGCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,338 control chromosomes in the GnomAD database, including 207 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.044 (207 hom., cov: 32)
• Consequence: XPA NM_000380.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796

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]

XPA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPA	NM_000380.4	c.173-496_173-493delGCAC		intron_variant		ENST00000375128.5	NP_000371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPA	ENST00000375128.5	c.173-496_173-493delGCAC		intron_variant		1	NM_000380.4	ENSP00000364270.5
XPA	ENST00000462523.5	n.173-496_173-493delGCAC		intron_variant		5		ENSP00000433006.1
XPA	ENST00000496104.1	n.73-496_73-493delGCAC		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6748 AN: 152220 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0443 AC: 6749 AN: 152338 Hom.: 207 Cov.: 32 AF XY: 0.0442 AC XY: 3292 AN XY: 74508

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0691

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0351 Hom.: 41

Bravo AF: 0.0388

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3176649; hg19: chr9-100456533;