ClinVar Miner

Submissions for variant NM_000081.4(LYST):c.10477T>C (p.Phe3493Leu)

gnomAD frequency: 0.00020  dbSNP: rs200511787
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000262603 SCV000355700 uncertain significance Chédiak-Higashi syndrome 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000262603 SCV001098993 likely benign Chédiak-Higashi syndrome 2024-12-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV000262603 SCV001520280 uncertain significance Chédiak-Higashi syndrome 2019-09-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002520467 SCV003698476 uncertain significance Inborn genetic diseases 2021-05-24 criteria provided, single submitter clinical testing The c.10477T>C (p.F3493L) alteration is located in exon 46 (coding exon 44) of the LYST gene. This alteration results from a T to C substitution at nucleotide position 10477, causing the phenylalanine (F) at amino acid position 3493 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005238867 SCV005887408 likely benign not specified 2025-01-13 criteria provided, single submitter clinical testing Variant summary: LYST c.10477T>C (p.Phe3493Leu) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 1607052 control chromosomes, predominantly at a frequency of 0.0039 within the Ashkenazi Jewish subpopulation in the gnomAD database (v4.1 dataset). The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 3.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in LYST causing Chediak-Higashi Syndrome phenotype (0.0011). To our knowledge, no occurrence of c.10477T>C in individuals affected with Chediak-Higashi Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 296355). Based on the evidence outlined above, the variant was classified as likely benign.

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