chr17-8121650-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001165967.2(HES7):c.614C>T(p.Pro205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000053 in 1,321,700 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 (★). Synonymous variant affecting the same amino acid position (i.e. P205P) has been classified as Likely benign.
Frequency
Consequence
NM_001165967.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HES7 | NM_001165967.2 | c.614C>T | p.Pro205Leu | missense_variant | 4/4 | ENST00000541682.7 | |
HES7 | NM_032580.4 | c.599C>T | p.Pro200Leu | missense_variant | 4/4 | ||
HES7 | XM_047436940.1 | c.710C>T | p.Pro237Leu | missense_variant | 3/3 | ||
HES7 | XM_047436941.1 | c.701C>T | p.Pro234Leu | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HES7 | ENST00000541682.7 | c.614C>T | p.Pro205Leu | missense_variant | 4/4 | 1 | NM_001165967.2 | A1 | |
HES7 | ENST00000317814.8 | c.599C>T | p.Pro200Leu | missense_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 33
GnomAD4 exome AF: 8.55e-7 AC: 1AN: 1169530Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 561958
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 22, 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1445685). 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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 200 of the HES7 protein (p.Pro200Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at