chr6-45914301-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_016929.5(CLIC5):c.515G>A(p.Arg172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,607,210 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R172W) has been classified as Uncertain significance.
Frequency
Consequence
NM_016929.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLIC5 | NM_016929.5 | c.515G>A | p.Arg172Gln | missense_variant | 5/6 | ENST00000339561.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLIC5 | ENST00000339561.12 | c.515G>A | p.Arg172Gln | missense_variant | 5/6 | 1 | NM_016929.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000979 AC: 149AN: 152170Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00147 AC: 366AN: 248992Hom.: 3 AF XY: 0.00149 AC XY: 201AN XY: 134528
GnomAD4 exome AF: 0.000751 AC: 1093AN: 1454922Hom.: 10 Cov.: 31 AF XY: 0.000761 AC XY: 551AN XY: 723768
GnomAD4 genome ? AF: 0.000978 AC: 149AN: 152288Hom.: 2 Cov.: 32 AF XY: 0.000833 AC XY: 62AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 13, 2019 | The p.Arg331Gln variant in CLIC5 is classified as benign because it has been identified in 3% (315/10342) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). Furthermore, >5 mammals (Chinese tree shrew, Lesser Egyptian jerboa, Prarie vole, Chinese hamster, golden hamster, mouse and rat) carry a glutamine (Gln) at this position despite high nearby amino acid conservation. ACMG/AMP Criteria applied: BA1, BP4_Strong. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at