3-14145540-AAACG-A

Variant names:

• chr3-14145540-AAACG-A
• rs3731180
• ENST00000608606.1:n.*57_*60delACGA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000608606.1(ENSG00000268279):​n.*57_*60delACGA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 700,274 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (17 hom.)
• Consequence: ENSG00000268279 ENST00000608606.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132
• Publications: 0 publications found

Genes affected

ENSG00000268279 (HGNC:):

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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 3-14145540-AAACG-A is Benign according to our data. Variant chr3-14145540-AAACG-A is described in ClinVar as [Likely_benign]. Clinvar id is 369401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5	c.*397_*400delCGTT		3_prime_UTR_variant	Exon 16 of 16	ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000268279	ENST00000608606.1	n.*57_*60delACGA		non_coding_transcript_exon_variant	Exon 4 of 5	5		ENSP00000476275.1
XPC	ENST00000285021.12	c.*397_*400delCGTT		3_prime_UTR_variant	Exon 16 of 16	1	NM_004628.5	ENSP00000285021.8
ENSG00000268279	ENST00000608606.1	n.*57_*60delACGA		3_prime_UTR_variant	Exon 4 of 5	5		ENSP00000476275.1

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152222 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00263 AC: 343 AN: 130462 AF XY: 0.00341

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000201

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00180 AC: 988 AN: 547934 Hom.: 17 AF XY: 0.00256 AC XY: 761 AN XY: 296718

African (AFR) AF: 0.00 AC: 0 AN: 15728

American (AMR) AF: 0.00 AC: 0 AN: 34706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20026

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32098

South Asian (SAS) AF: 0.0152 AC: 948 AN: 62568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33192

Middle Eastern (MID) AF: 0.000409 AC: 1 AN: 2444

European-Non Finnish (NFE) AF: 0.0000158 AC: 5 AN: 316758

Other (OTH) AF: 0.00109 AC: 33 AN: 30414

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152340 Hom.: 2 Cov.: 32 AF XY: 0.000805 AC XY: 60 AN XY: 74510

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000136

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arrhythmogenic right ventricular cardiomyopathy Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13
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: rs3731180; hg19: chr3-14187040;