chr13-102875652-G-C

Position:

chr13-102875652-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.3310G>C(p.Asp1104His) variant causes a missense change. The variant allele was found at a frequency of 0.243 in 1,613,874 control chromosomes in the GnomAD database, including 52,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7842 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44770 hom. )

Consequence

ERCC5
NM_000123.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 5.18

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:):

BIVM-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=2.9867887E-4).

BP6

Variant 13-102875652-G-C is Benign according to our data. Variant chr13-102875652-G-C is described in ClinVar as [Benign]. Clinvar id is 129011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102875652-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 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.3310G>C	p.Asp1104His	missense_variant	15/15	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2 linkuse as main transcript	c.4672G>C	p.Asp1558His	missense_variant	23/23		NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2 linkuse as main transcript	c.3310G>C	p.Asp1104His	missense_variant	15/15		NM_000123.4	ENSP00000498881	P1	P28715-1

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

45995

AN:

151936

Hom.:

7831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.278

AC:

69697

AN:

251078

Hom.:

10863

AF XY:

0.267

AC XY:

36243

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.494

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.237

AC:

346299

AN:

1461818

Hom.:

44770

Cov.:

AF XY:

0.235

AC XY:

171187

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.529

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.303

AC:

46051

AN:

152056

Hom.:

7842

Cov.:

AF XY:

0.303

AC XY:

22496

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.453

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.492

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.244

Hom.:

3790

Bravo

AF:

0.320

TwinsUK

AF:

0.207

AC:

766

ALSPAC

AF:

0.210

AC:

809

ESP6500AA

AF:

0.456

AC:

2009

ESP6500EA

AF:

0.229

AC:

1968

ExAC

AF:

0.277

AC:

33673

Asia WGS

AF:

0.388

AC:

1348

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group G

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 16738949, 21390047, 24728327, 22815677, 14729591, 27153395, 24802942) -

not specified

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -

Cerebrooculofacioskeletal syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

.;.;.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.026

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.32

T;T;.;T;T

MetaRNN

Benign

0.00030

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

2.0

.;.;.;M;.

MutationTaster

Benign

0.0037

P;P

PROVEAN

Uncertain

-3.1

.;.;.;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0040

.;.;.;D;T

Sift4G

Uncertain

0.037

.;.;.;D;T

Polyphen

0.99

.;.;.;D;.

Vest4

0.29, 0.25

MPC

0.52

ClinPred

0.017

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.26

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