rs587778291

Variant names:

• chr13-102875580-GG-CA
• rs587778291
• NM_000123.4:c.3238_3239delGGinsCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000123.4(ERCC5):​c.3238_3239delGGinsCA​(p.Gly1080Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.000835 in 235 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1080R) has been classified as Benign.

• Frequency: GnomAD MNV: 𝑓 0.00083 Genomes: not found (cov: 33)
• Consequence: ERCC5 NM_000123.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.162
• Publications: 1 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 -8 ACMG points.

• BP6: Variant 13-102875580-GG-CA is Benign according to our data. Variant chr13-102875580-GG-CA is described in ClinVar as Likely_benign. ClinVar VariationId is 2162960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.3238_3239delGGinsCA	p.Gly1080Gln	missense_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4600_4601delGGinsCA	p.Gly1534Gln	missense_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.3238_3239delGGinsCA	p.Gly1080Gln	missense_variant			NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4600_4601delGGinsCA	p.Gly1534Gln	missense_variant		5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3913_3914delGGinsCA	p.Gly1305Gln	missense_variant		5		ENSP00000492684.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.000835 AC: 235 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 11, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: ERCC5 c.3238_3239delinsCA (p.Gly1080Gln) results in a non-conservative amino acid change in the encoded protein sequence. One of two in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00083 in 281534 control chromosomes, predominantly at a frequency of 0.0069 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in ERCC5 causing Cerebrooculofacioskeletal Syndrome 3 phenotype. To our knowledge, no occurrence of c.3238_3239delinsCA in individuals affected with Cerebrooculofacioskeletal Syndrome 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2162960). Based on the evidence outlined above, the variant was classified as likely benign. -

not provided Benign:1

May 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs587778291; hg19: chr13-103527930;