NM_000123.4:c.138T>C

Variant names:

• chr13-102852167-T-C
• rs1047768
• NM_000123.4:c.138T>C

Variant summary

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

The NM_000123.4(ERCC5):​c.138T>C​(p.His46His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,696 control chromosomes in the GnomAD database, including 273,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26664 hom., cov: 32)
  • Exomes 𝑓: 0.57 (246624 hom.)
• Consequence: ERCC5 NM_000123.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.00400
• Publications: 142 publications found

Genes affected

ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

BIVM-ERCC5 (HGNC:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 13-102852167-T-C is Benign according to our data. Variant chr13-102852167-T-C is described in ClinVar as Benign. ClinVar VariationId is 129009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000123.4. 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
	ERCC5	NM_000123.4	MANE Select	c.138T>C	p.His46His	synonymous	Exon 2 of 15	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.1500T>C	p.His500His	synonymous	Exon 10 of 23	NP_001191354.2	R4GMW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	ENST00000652225.2	MANE Select	c.138T>C	p.His46His	synonymous	Exon 2 of 15	ENSP00000498881.2	P28715-1
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.1500T>C	p.His500His	synonymous	Exon 12 of 25	ENSP00000491742.1	R4GMW8
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.813T>C	p.His271His	synonymous	Exon 11 of 24	ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88613 AN: 151876 Hom.: 26615 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.568

GnomAD2 exomes AF: 0.520 AC: 130641 AN: 251366 AF XY: 0.527

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.264

Gnomad FIN exome AF: 0.619

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.574 AC: 839091 AN: 1461702 Hom.: 246624 Cov.: 56 AF XY: 0.573 AC XY: 416387 AN XY: 727164

African (AFR) AF: 0.668 AC: 22379 AN: 33478

American (AMR) AF: 0.310 AC: 13851 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 15066 AN: 26130

East Asian (EAS) AF: 0.224 AC: 8872 AN: 39680

South Asian (SAS) AF: 0.501 AC: 43205 AN: 86244

European-Finnish (FIN) AF: 0.613 AC: 32755 AN: 53404

Middle Eastern (MID) AF: 0.523 AC: 3017 AN: 5766

European-Non Finnish (NFE) AF: 0.599 AC: 665792 AN: 1111904

Other (OTH) AF: 0.566 AC: 34154 AN: 60382

GnomAD4 genome AF: 0.584 AC: 88713 AN: 151994 Hom.: 26664 Cov.: 32 AF XY: 0.580 AC XY: 43078 AN XY: 74280

African (AFR) AF: 0.665 AC: 27556 AN: 41442

American (AMR) AF: 0.426 AC: 6506 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1289 AN: 5178

South Asian (SAS) AF: 0.495 AC: 2384 AN: 4818

European-Finnish (FIN) AF: 0.623 AC: 6552 AN: 10516

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40504 AN: 67976

Other (OTH) AF: 0.571 AC: 1204 AN: 2110

Alfa AF: 0.578 Hom.: 110292

Bravo AF: 0.569

Asia WGS AF: 0.406 AC: 1415 AN: 3478

EpiCase AF: 0.584

EpiControl AF: 0.586

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	Xeroderma pigmentosum, group G (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.10
DANN	Benign	0.33
PhyloP100		-0.0040
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: rs1047768; hg19: chr13-103504517; COSMIC: COSV63245576;