12-119179323-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014365.3(HSPB8):c.11G>A(p.Gly4Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,454 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G4S) has been classified as Uncertain significance.
Frequency
Consequence
NM_014365.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPB8 | NM_014365.3 | c.11G>A | p.Gly4Asp | missense_variant | 1/3 | ENST00000281938.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPB8 | ENST00000281938.7 | c.11G>A | p.Gly4Asp | missense_variant | 1/3 | 1 | NM_014365.3 | P1 | |
HSPB8 | ENST00000674542.1 | c.11G>A | p.Gly4Asp | missense_variant | 1/2 | ||||
HSPB8 | ENST00000676244.1 | n.73+5325G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250536Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135646
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461454Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727078
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2L Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with HSPB8-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 4 of the HSPB8 protein (p.Gly4Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at