17-8121659-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_001165967.2(HES7):āc.605T>Cā(p.Leu202Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000599 in 1,169,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001165967.2 missense
Scores
Clinical Significance
Conservation
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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.605T>C | p.Leu202Pro | missense_variant | 4/4 | ENST00000541682.7 | |
HES7 | NM_032580.4 | c.590T>C | p.Leu197Pro | missense_variant | 4/4 | ||
HES7 | XM_047436940.1 | c.701T>C | p.Leu234Pro | missense_variant | 3/3 | ||
HES7 | XM_047436941.1 | c.692T>C | p.Leu231Pro | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HES7 | ENST00000541682.7 | c.605T>C | p.Leu202Pro | missense_variant | 4/4 | 1 | NM_001165967.2 | A1 | |
HES7 | ENST00000317814.8 | c.590T>C | p.Leu197Pro | missense_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000599 AC: 7AN: 1169516Hom.: 0 Cov.: 30 AF XY: 0.00000712 AC XY: 4AN XY: 562022
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 17, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 197 of the HES7 protein (p.Leu197Pro). This variant is not present in population databases (gnomAD no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with HES7-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.