chr6-45903105-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP3BP4_ModerateBP6
The NM_016929.5(CLIC5):c.739C>T(p.Arg247Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016929.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000342 AC: 86AN: 251326Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135816
GnomAD4 exome AF: 0.000112 AC: 163AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.0000949 AC XY: 69AN XY: 727236
GnomAD4 genome AF: 0.000118 AC: 18AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74476
ClinVar
Submissions by phenotype
not provided Benign:2
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not specified Uncertain:1
The p.Arg406Cys variant in CLIC5 has not been previously reported in individuals with hearing loss but has been identified in 0.2% (75/35430) of Latino chromoso mes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, tho ugh this information is not predictive enough to determine pathogenicity. In sum mary, the clinical significance of the p.Arg406Cys variant is uncertain. ACMG/AM P Criteria applied: BS1_Supporting, PP3. -
CLIC5-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at