17-63917497-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS1_Supporting
The NM_000515.5(GH1):c.466G>T(p.Asp156Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,828 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 (★). Synonymous variant affecting the same amino acid position (i.e. D156D) has been classified as Likely benign.
Frequency
Consequence
NM_000515.5 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 |
---|---|---|---|---|---|---|---|
GH1 | NM_000515.5 | c.466G>T | p.Asp156Tyr | missense_variant | 5/5 | ENST00000323322.10 | |
LOC112268204 | XR_002958148.2 | n.341-100C>A | intron_variant, non_coding_transcript_variant | ||||
GH1 | NM_022559.4 | c.421G>T | p.Asp141Tyr | missense_variant | 5/5 | ||
GH1 | NM_022560.4 | c.346G>T | p.Asp116Tyr | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GH1 | ENST00000323322.10 | c.466G>T | p.Asp156Tyr | missense_variant | 5/5 | 1 | NM_000515.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251170Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135738
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727144
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2022 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with GH1-related conditions. This variant is present in population databases (rs770336766, gnomAD 0.06%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 156 of the GH1 protein (p.Asp156Tyr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at