NM_004628.5:c.2033+289T>C

Variant names:

• chr3-14156046-A-G
• rs3731143
• NM_004628.5:c.2033+289T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004628.5(XPC):​c.2033+289T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,184 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (171 hom., cov: 32)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.33
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-14156046-A-G is Benign according to our data. Variant chr3-14156046-A-G is described in ClinVar as Benign. ClinVar VariationId is 1273262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPC	NM_004628.5	MANE Select	c.2033+289T>C		intron	N/A	NP_004619.3
	XPC	NM_001354727.2		c.1872+1965T>C		intron	N/A	NP_001341656.1
	XPC	NM_001354729.2		c.2015+289T>C		intron	N/A	NP_001341658.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPC	ENST00000285021.12	TSL:1 MANE Select	c.2033+289T>C		intron	N/A	ENSP00000285021.8
	XPC	ENST00000476581.6	TSL:1	n.*1486+289T>C		intron	N/A	ENSP00000424548.1
	XPC	ENST00000850575.1		c.1872+1965T>C		intron	N/A	ENSP00000520865.1

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6046 AN: 152066 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0585

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0397 AC: 6045 AN: 152184 Hom.: 171 Cov.: 32 AF XY: 0.0395 AC XY: 2942 AN XY: 74400

African (AFR) AF: 0.0110 AC: 456 AN: 41506

American (AMR) AF: 0.0460 AC: 703 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0353 AC: 170 AN: 4820

European-Finnish (FIN) AF: 0.0298 AC: 315 AN: 10588

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0585 AC: 3978 AN: 68008

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0474 Hom.: 111

Bravo AF: 0.0384

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.026
DANN	Benign	0.56
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

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: rs3731143; hg19: chr3-14197546;