ClinVar Miner

Submissions for variant NM_005236.3(ERCC4):c.1102G>A (p.Glu368Lys)

gnomAD frequency: 0.00024  dbSNP: rs148933357
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001316070 SCV001506672 uncertain significance Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q 2022-01-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 368 of the ERCC4 protein (p.Glu368Lys). This variant is present in population databases (rs148933357, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1016989). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV002258194 SCV002537720 uncertain significance Xeroderma pigmentosum 2022-02-13 criteria provided, single submitter curation
Ambry Genetics RCV002545088 SCV003586101 uncertain significance Inborn genetic diseases 2021-12-20 criteria provided, single submitter clinical testing The c.1102G>A (p.E368K) alteration is located in exon 6 (coding exon 6) of the ERCC4 gene. This alteration results from a G to A substitution at nucleotide position 1102, causing the glutamic acid (E) at amino acid position 368 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003145559 SCV003833570 uncertain significance not provided 2021-09-06 criteria provided, single submitter clinical testing
GeneDx RCV003145559 SCV005327418 uncertain significance not provided 2023-06-21 criteria provided, single submitter clinical testing Alters the last nucleotide of the exon and is predicted to destroy the splice donor site and result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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