rs3176639

Positions:

• chr9-97695827-C-A

Variant summary

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

The NM_000380.4(XPA):​c.172+1294G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,162 control chromosomes in the GnomAD database, including 4,595 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 0.22 (4595 hom., cov: 32)
• Consequence: XPA NM_000380.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPA	NM_000380.4	c.172+1294G>T		intron_variant		ENST00000375128.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPA	ENST00000375128.5	c.172+1294G>T		intron_variant		1	NM_000380.4	P1
XPA	ENST00000462523.5	c.172+1294G>T		intron_variant, NMD_transcript_variant		5
XPA	ENST00000496104.1	n.72+1397G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33772 AN: 152044 Hom.: 4594 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.222 AC: 33765 AN: 152162 Hom.: 4595 Cov.: 32 AF XY: 0.219 AC XY: 16265 AN XY: 74390

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.228

Alfa AF: 0.278 Hom.: 3272

Bravo AF: 0.212

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
DANN	Benign	0.68

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: rs3176639; hg19: chr9-100458109;