rs9514067

Positions:

• chr13-102875580-G-A
• chr13-102875580-G-C
• chr13-102875580-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000123.4(ERCC5):​c.3238G>A​(p.Gly1080Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1080E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERCC5 NM_000123.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03876385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC5	NM_000123.4	c.3238G>A	p.Gly1080Arg	missense_variant	15/15	ENST00000652225.2
BIVM-ERCC5	NM_001204425.2	c.4600G>A	p.Gly1534Arg	missense_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC5	ENST00000652225.2	c.3238G>A	p.Gly1080Arg	missense_variant	15/15		NM_000123.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460808 Hom.: 0 Cov.: 86 AF XY: 0.00 AC XY: 0 AN XY: 726676

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.53
DANN	Benign	0.61
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.48	T;T;.;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.039	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N
Polyphen		0.0	.;.;.;B;.
Vest4		0.014, 0.033
MutPred		0.24		.;.;.;Gain of catalytic residue at K1079 (P = 0.011);.;
MVP		0.16
MPC		0.14
ClinPred		0.050	T
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

Other links and lift over

dbSNP: rs9514067; hg19: chr13-103527930;