ClinVar Miner

Submissions for variant NM_002272.4(KRT4):c.364C>G (p.Leu122Val)

gnomAD frequency: 0.00007  dbSNP: rs758695571
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000406551 SCV000380142 uncertain significance White sponge nevus 1 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV003258756 SCV003975489 uncertain significance Inborn genetic diseases 2023-03-17 criteria provided, single submitter clinical testing The c.364C>G (p.L122V) alteration is located in exon 1 (coding exon 1) of the KRT4 gene. This alteration results from a C to G substitution at nucleotide position 364, causing the leucine (L) at amino acid position 122 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000406551 SCV001549414 likely benign White sponge nevus 1 no assertion criteria provided clinical testing The KRT4 p.L122V variant was not identified in the literature but was identified in dbSNP (ID: rs758695571) and ClinVar (classified as uncertain significance by Illumina). The variant was identified in control databases in 40 of 279118 chromosomes at a frequency of 0.0001433, and was observed at the highest frequency in the East Asian population in 39 of 19780 chromosomes (freq: 0.001972) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.L122 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome, Splice AI genome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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