rs2307491

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000123.4(ERCC5):c.932C>G(p.Ser311Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ERCC5
NM_000123.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 4.20

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029830098).

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.932C>G	p.Ser311Cys	missense	Exon 8 of 15	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.2294C>G	p.Ser765Cys	missense	Exon 16 of 23	NP_001191354.2	R4GMW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERCC5	ENST00000652225.2	MANE Select	c.932C>G	p.Ser311Cys	missense	Exon 8 of 15	ENSP00000498881.2	P28715-1
BIVM-ERCC5	ENST00000639435.1	TSL:5	c.2294C>G	p.Ser765Cys	missense	Exon 18 of 25	ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1	TSL:5	c.1607C>G	p.Ser536Cys	missense	Exon 17 of 24	ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.0000876

AC:

AN:

251248

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.00123

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:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.000116

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000341

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000339

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome (1)

Inborn genetic diseases (1)

not provided (1)

Xeroderma pigmentosum, group G (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.22

Eigen

Benign

-0.093

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.68

M_CAP

Benign

0.0043

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

4.2

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.024

Sift

Benign

0.036

Sift4G

Benign

0.20

Polyphen

0.062

Vest4

0.14

MVP

0.39

MPC

0.13

ClinPred

0.10

GERP RS

3.9

Varity_R

0.16

gMVP

0.28

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over