chr6-35814627-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_182548.4(LHFPL5):c.494C>T(p.Thr165Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_182548.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251392Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135884
GnomAD4 exome AF: 0.000118 AC: 173AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000113 AC XY: 82AN XY: 727248
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74300
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 67 Pathogenic:2
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not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23217710, 27260575, 31835641, 16752389) -
LHFPL5-related disorder Uncertain:1
The LHFPL5 c.494C>T variant is predicted to result in the amino acid substitution p.Thr165Met. This variant was reported in the homozygous state in six individuals from a consanguineous family with nonsyndromic hearing loss (Kalay. 2006. PubMed ID: 16752389). This variant is reported in 0.0096% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at