17-8121698-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_001165967.2(HES7):c.566C>T(p.Ala189Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001165967.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HES7 | NM_001165967.2 | c.566C>T | p.Ala189Val | missense_variant | 4/4 | ENST00000541682.7 | |
HES7 | NM_032580.4 | c.551C>T | p.Ala184Val | missense_variant | 4/4 | ||
HES7 | XM_047436940.1 | c.662C>T | p.Ala221Val | missense_variant | 3/3 | ||
HES7 | XM_047436941.1 | c.653C>T | p.Ala218Val | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HES7 | ENST00000541682.7 | c.566C>T | p.Ala189Val | missense_variant | 4/4 | 1 | NM_001165967.2 | A1 | |
HES7 | ENST00000317814.8 | c.551C>T | p.Ala184Val | missense_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152128Hom.: 0 Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1178236Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 566862
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1362098). This variant has not been reported in the literature in individuals affected with HES7-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 184 of the HES7 protein (p.Ala184Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at