rs3176646

Positions:

• chr9-97694479-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000375128.5(XPA):​c.173-720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,324 control chromosomes in the GnomAD database, including 101 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 0.032 (101 hom., cov: 33)
• Consequence: XPA ENST00000375128.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0321 (4883/152324) while in subpopulation NFE AF= 0.0501 (3407/68008). AF 95% confidence interval is 0.0487. There are 101 homozygotes in gnomad4. There are 2310 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPA	NM_000380.4	c.173-720C>T		intron_variant		ENST00000375128.5	NP_000371.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPA	ENST00000375128.5	c.173-720C>T		intron_variant		1	NM_000380.4	ENSP00000364270	P1
XPA	ENST00000462523.5	c.173-720C>T		intron_variant, NMD_transcript_variant		5		ENSP00000433006
XPA	ENST00000496104.1	n.73-720C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4884 AN: 152206 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.00863

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0321 AC: 4883 AN: 152324 Hom.: 101 Cov.: 33 AF XY: 0.0310 AC XY: 2310 AN XY: 74482

Gnomad4 AFR AF: 0.00861

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00766

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0346 Hom.: 16

Bravo AF: 0.0317

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.62
DANN	Benign	0.61

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: rs3176646; hg19: chr9-100456761;