13-102875580-G-C

Position:

chr13-102875580-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.260

Variant links:

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]

ERCC5 links:

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]

BIVM-ERCC5 links:

ERCC5 (HGNC:):

ERCC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 134173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102875580-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4 linkuse as main transcript	c.3238G>C	p.Gly1080Arg	missense_variant	15/15	ENST00000652225.2	NP_000114.3	P28715-1
BIVM-ERCC5	NM_001204425.2 linkuse as main transcript	c.4600G>C	p.Gly1534Arg	missense_variant	23/23		NP_001191354.2	R4GMW8Q59FZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ERCC5	ENST00000652225.2 linkuse as main transcript	c.3238G>C	p.Gly1080Arg	missense_variant	15/15		NM_000123.4	ENSP00000498881.2	P28715-1
BIVM-ERCC5	ENST00000639435.1 linkuse as main transcript	c.4600G>C	p.Gly1534Arg	missense_variant	25/25	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 linkuse as main transcript	c.3913G>C	p.Gly1305Arg	missense_variant	24/24	5		ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

151936

AN:

152250

Hom.:

75812

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.999

AC:

250311

AN:

250462

Hom.:

125080

AF XY:

0.999

AC XY:

135312

AN XY:

135382

show subpopulations

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 SAS exome

AF:

0.999

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.:

AF XY:

1.00

AC XY:

726510

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.994

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

AF:

0.998

AC:

152056

AN:

152368

Hom.:

75873

Cov.:

AF XY:

0.998

AC XY:

74349

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.993

Gnomad4 AMR

AF:

0.999

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.999

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:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.73

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

LIST_S2

Benign

0.48

T;T;.;T;T

MetaRNN

Benign

8.6e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

.;.;.;N;.

PROVEAN

Benign

0.35

.;.;.;N;N

REVEL

Benign

0.015

Sift

Benign

0.59

.;.;.;T;T

Sift4G

Benign

0.53

.;.;.;T;T

Polyphen

0.0

.;.;.;B;.

Vest4

0.014, 0.033

MutPred

0.24

.;.;.;Gain of catalytic residue at K1079 (P = 0.011);.;

MPC

0.14

ClinPred

0.00055

GERP RS

0.14

Varity_R

0.020

gMVP

0.13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over