rs150063353
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BS2_Supporting
The NM_182961.4(SYNE1):c.20182C>T(p.Arg6728Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R6728H) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 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 |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.20182C>T | p.Arg6728Cys | missense_variant | 109/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.20182C>T | p.Arg6728Cys | missense_variant | 109/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.19969C>T | p.Arg6657Cys | missense_variant | 108/146 | 1 | |||
SYNE1 | ENST00000367256.9 | n.3874C>T | non_coding_transcript_exon_variant | 24/61 | 1 | ||||
SYNE1 | ENST00000409694.6 | n.3766C>T | non_coding_transcript_exon_variant | 22/59 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251436Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135900
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727234
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | SYNE1: PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 25, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 15, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 04, 2016 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 440314). This variant is also known as p.R6728C. This missense change has been observed in individual(s) with clinical features of autosomal recessive spastic ataxia (PMID: 29482223). This variant is present in population databases (rs150063353, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 6657 of the SYNE1 protein (p.Arg6657Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at