Variant 9-97675203-CTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000380.4(XPA):c.*234_*235del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 633,756 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 2 hom. )

Consequence

XPA
NM_000380.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.569

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPA	NM_000380.4 linkuse as main transcript	c.234_235del		3_prime_UTR_variant	6/6	ENST00000375128.5	NP_000371.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
XPA	ENST00000375128.5 linkuse as main transcript	c.234_235del	3_prime_UTR_variant	6/6	1	NM_000380.4	ENSP00000364270	P1
XPA	ENST00000485042.1 linkuse as main transcript	n.568_569del	non_coding_transcript_exon_variant	2/2	3
XPA	ENST00000462523.5 linkuse as main transcript	c.492_493del	3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000433006

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00234

AC:

307

AN:

131102

Hom.:

AF XY:

0.00231

AC XY:

165

AN XY:

71456

show subpopulations

Gnomad AFR exome

AF:

0.000487

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00361

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000583

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00398

Gnomad OTH exome

AF:

0.00225

GnomAD4 exome

AF:

0.00256

AC:

1233

AN:

481444

Hom.:

AF XY:

0.00259

AC XY:

678

AN XY:

261972

show subpopulations

Gnomad4 AFR exome

AF:

0.000410

Gnomad4 AMR exome

AF:

0.00240

Gnomad4 ASJ exome

AF:

0.00308

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000554

Gnomad4 FIN exome

AF:

0.000178

Gnomad4 NFE exome

AF:

0.00353

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00176

AC:

268

AN:

152312

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00192

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Xeroderma pigmentosum

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over