chr3-14145330-A-T

Variant names:

• chr3-14145330-A-T
• rs2470352
• NM_004628.5:c.*611T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004628.5(XPC):​c.*611T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 697,562 control chromosomes in the GnomAD database, including 12,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2412 hom., cov: 32)
  • Exomes 𝑓: 0.17 (9634 hom.)
• Consequence: XPC NM_004628.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.63
• Publications: 15 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]

ENSG00000268279 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 3-14145330-A-T is Benign according to our data. Variant chr3-14145330-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 343552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 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.*611T>A		3_prime_UTR	Exon 16 of 16	NP_004619.3
	XPC	NM_001354727.2		c.*611T>A		3_prime_UTR	Exon 16 of 16	NP_001341656.1	A0ABB0MVJ4
	XPC	NM_001354729.2		c.*611T>A		3_prime_UTR	Exon 16 of 16	NP_001341658.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPC	ENST00000285021.12	TSL:1 MANE Select	c.*611T>A		3_prime_UTR	Exon 16 of 16	ENSP00000285021.8	Q01831-1
	ENSG00000268279	ENST00000608606.1	TSL:5	n.244A>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000476275.1	V9GY05
	XPC	ENST00000850575.1		c.*611T>A		3_prime_UTR	Exon 16 of 16	ENSP00000520865.1	A0ABB0MVJ4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25257 AN: 151652 Hom.: 2412 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.151 AC: 19384 AN: 128366 AF XY: 0.151

Gnomad AFR exome AF: 0.0907

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.000290

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.175 AC: 95373 AN: 545792 Hom.: 9634 Cov.: 0 AF XY: 0.173 AC XY: 50986 AN XY: 295454

African (AFR) AF: 0.0963 AC: 1501 AN: 15594

American (AMR) AF: 0.120 AC: 4114 AN: 34206

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4016 AN: 19972

East Asian (EAS) AF: 0.000249 AC: 8 AN: 32094

South Asian (SAS) AF: 0.104 AC: 6431 AN: 62004

European-Finnish (FIN) AF: 0.233 AC: 7742 AN: 33176

Middle Eastern (MID) AF: 0.158 AC: 384 AN: 2436

European-Non Finnish (NFE) AF: 0.208 AC: 65784 AN: 315974

Other (OTH) AF: 0.178 AC: 5393 AN: 30336

GnomAD4 genome AF: 0.166 AC: 25257 AN: 151770 Hom.: 2412 Cov.: 32 AF XY: 0.164 AC XY: 12195 AN XY: 74146

African (AFR) AF: 0.0967 AC: 4001 AN: 41372

American (AMR) AF: 0.156 AC: 2381 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.0956 AC: 461 AN: 4822

European-Finnish (FIN) AF: 0.239 AC: 2503 AN: 10488

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14419 AN: 67908

Other (OTH) AF: 0.190 AC: 398 AN: 2100

Alfa AF: 0.125 Hom.: 306

Bravo AF: 0.158

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Arrhythmogenic right ventricular cardiomyopathy (1)
-	-	1	not provided (1)
-	-	1	Xeroderma pigmentosum (1)
-	-	1	Xeroderma pigmentosum, group C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.1
DANN	Benign	0.69
PhyloP100		1.6
Mutation Taster		=100/0	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: rs2470352; hg19: chr3-14186830;