9-97682669-C-G

Position:

• chr9-97682669-C-G

Variant summary

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

The NM_000380.4(XPA):​c.673+2254G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 152,148 control chromosomes in the GnomAD database, including 731 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 0.086 (731 hom., cov: 32)
• Consequence: XPA NM_000380.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPA	NM_000380.4	c.673+2254G>C		intron_variant		ENST00000375128.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPA	ENST00000375128.5	c.673+2254G>C		intron_variant		1	NM_000380.4	P1
XPA	ENST00000462523.5	c.674-239G>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 13096 AN: 152030 Hom.: 725 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0862 AC: 13110 AN: 152148 Hom.: 731 Cov.: 32 AF XY: 0.0882 AC XY: 6559 AN XY: 74382

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0716

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0923 Hom.: 102

Bravo AF: 0.0800

Asia WGS AF: 0.114 AC: 396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.71

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: rs2805835; hg19: chr9-100444951;