rs2958057

Variant names:

• chr3-14156487-A-T
• rs2958057
• NM_004628.5:c.1881T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-14156487-A-T
• chr3-14156487-A-C
• chr3-14156487-A-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004628.5(XPC):​c.1881T>A​(p.Ala627Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,614,016 control chromosomes in the GnomAD database, including 807,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (76193 hom., cov: 34)
  • Exomes 𝑓: 1.0 (730815 hom.)
• Consequence: XPC NM_004628.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.38
• Publications: 25 publications found

Genes affected

XPC (HGNC:12816): (XPC complex subunit, DNA damage recognition and repair factor) The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]

XPC-AS1 (HGNC:55014): (XPC antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-14156487-A-T is Benign according to our data. Variant chr3-14156487-A-T is described in ClinVar as Benign. ClinVar VariationId is 190212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPC	NM_004628.5	MANE Select	c.1881T>A	p.Ala627Ala	synonymous	Exon 10 of 16	NP_004619.3
	XPC	NM_001354729.2		c.1863T>A	p.Ala621Ala	synonymous	Exon 10 of 16	NP_001341658.1
	XPC	NM_001354730.2		c.1635T>A	p.Ala545Ala	synonymous	Exon 10 of 16	NP_001341659.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPC	ENST00000285021.12	TSL:1 MANE Select	c.1881T>A	p.Ala627Ala	synonymous	Exon 10 of 16	ENSP00000285021.8	Q01831-1
	XPC	ENST00000476581.6	TSL:1	n.*1334T>A		non_coding_transcript_exon	Exon 9 of 15	ENSP00000424548.1	Q01831-3
	XPC	ENST00000476581.6	TSL:1	n.*1334T>A		3_prime_UTR	Exon 9 of 15	ENSP00000424548.1	Q01831-3

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152268 AN: 152268 Hom.: 76134 Cov.: 34

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 249140 AN: 249140 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1461630 AN: 1461630 Hom.: 730815 Cov.: 73 AF XY: 1.00 AC XY: 727086 AN XY: 727086

African (AFR) AF: 1.00 AC: 33476 AN: 33476

American (AMR) AF: 1.00 AC: 44710 AN: 44710

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26134 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39698

South Asian (SAS) AF: 1.00 AC: 86242 AN: 86242

European-Finnish (FIN) AF: 1.00 AC: 53394 AN: 53394

Middle Eastern (MID) AF: 1.00 AC: 5768 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111834 AN: 1111834

Other (OTH) AF: 1.00 AC: 60374 AN: 60374

GnomAD4 genome AF: 1.00 AC: 152386 AN: 152386 Hom.: 76193 Cov.: 34 AF XY: 1.00 AC XY: 74520 AN XY: 74520

African (AFR) AF: 1.00 AC: 41594 AN: 41594

American (AMR) AF: 1.00 AC: 15312 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68046 AN: 68046

Other (OTH) AF: 1.00 AC: 2112 AN: 2112

Alfa AF: 1.00 Hom.: 13791

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Xeroderma pigmentosum, group C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2958057; hg19: chr3-14197987; COSMIC: COSV53205858; COSMIC: COSV53205858;