rs757688642
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS2_Supporting
The NM_182961.4(SYNE1):c.21469C>T(p.Arg7157Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,858 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. R7157H) has been classified as Likely benign.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.21469C>T | p.Arg7157Cys | missense_variant | 117/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.21469C>T | p.Arg7157Cys | missense_variant | 117/146 | 1 | NM_182961.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251256Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135776
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727180
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74278
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 26, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 05, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 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: "Benign"; Align-GVGD: "Class C0". The cysteine 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: 576512). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is present in population databases (rs757688642, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 7086 of the SYNE1 protein (p.Arg7086Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at