13-102875580-G-C

Variant names:

• chr13-102875580-G-C
• rs9514067
• NM_000123.4:c.3238G>C

Variant summary

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

The NM_000123.4(ERCC5):​c.3238G>C​(p.Gly1080Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,613,176 control chromosomes in the GnomAD database, including 805,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1080Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 1.0 (75873 hom., cov: 33)
  • Exomes 𝑓: 1.0 (730055 hom.)
• Consequence: ERCC5 NM_000123.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.260
• Publications: 54 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.625595E-7).
• BP6: Variant 13-102875580-G-C is Benign according to our data. Variant chr13-102875580-G-C is described in ClinVar as Benign. ClinVar VariationId is 134173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	NM_000123.4	MANE Select	c.3238G>C	p.Gly1080Arg	missense	Exon 15 of 15	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.4600G>C	p.Gly1534Arg	missense	Exon 23 of 23	NP_001191354.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	ENST00000652225.2	MANE Select	c.3238G>C	p.Gly1080Arg	missense	Exon 15 of 15	ENSP00000498881.2
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.4600G>C	p.Gly1534Arg	missense	Exon 25 of 25	ENSP00000491742.1
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.3913G>C	p.Gly1305Arg	missense	Exon 24 of 24	ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151936 AN: 152250 Hom.: 75812 Cov.: 33

Gnomad AFR AF: 0.993

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD2 exomes AF: 0.999 AC: 250311 AN: 250462 AF XY: 0.999

Gnomad AFR exome AF: 0.994

Gnomad AMR exome AF: 0.999

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: 1460458 AN: 1460808 Hom.: 730055 Cov.: 86 AF XY: 1.00 AC XY: 726510 AN XY: 726676

African (AFR) AF: 0.994 AC: 33135 AN: 33334

American (AMR) AF: 0.999 AC: 44487 AN: 44514

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26109 AN: 26110

East Asian (EAS) AF: 1.00 AC: 39696 AN: 39698

South Asian (SAS) AF: 1.00 AC: 85960 AN: 85998

European-Finnish (FIN) AF: 1.00 AC: 53410 AN: 53410

Middle Eastern (MID) AF: 1.00 AC: 5764 AN: 5764

European-Non Finnish (NFE) AF: 1.00 AC: 1111621 AN: 1111664

Other (OTH) AF: 0.999 AC: 60276 AN: 60316

GnomAD4 genome AF: 0.998 AC: 152056 AN: 152368 Hom.: 75873 Cov.: 33 AF XY: 0.998 AC XY: 74349 AN XY: 74506

African (AFR) AF: 0.993 AC: 41307 AN: 41590

American (AMR) AF: 0.999 AC: 15291 AN: 15306

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

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.999 AC: 4825 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

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

European-Non Finnish (NFE) AF: 1.00 AC: 68042 AN: 68046

Other (OTH) AF: 0.999 AC: 2113 AN: 2116

Alfa AF: 0.927 Hom.: 46084

Bravo AF: 0.998

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.993 AC: 4373

ESP6500EA AF: 1.00 AC: 8600

ExAC AF: 0.999 AC: 121328

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.43
DANN	Benign	0.63
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	8.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.26
PROVEAN	Benign	0.35	N
REVEL	Benign	0.015
Sift	Benign	0.59	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.014
MutPred		0.24		Gain of catalytic residue at K1079 (P = 0.011)
MPC		0.14
ClinPred		0.00055	T
GERP RS		0.14
Varity_R		0.020
gMVP		0.13
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: rs9514067; hg19: chr13-103527930; COSMIC: COSV107450835; COSMIC: COSV107450835;