rs141883764
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_182961.4(SYNE1):c.14501G>A(p.Arg4834Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,614,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.14501G>A | p.Arg4834Gln | missense_variant | 78/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.14501G>A | p.Arg4834Gln | missense_variant | 78/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.14288G>A | p.Arg4763Gln | missense_variant | 77/146 | 1 | |||
SYNE1 | ENST00000490135.6 | n.1847G>A | non_coding_transcript_exon_variant | 2/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000361 AC: 55AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251438Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135888
GnomAD4 exome AF: 0.000177 AC: 259AN: 1461890Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 127AN XY: 727248
GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 30, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 21, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 11, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.14288G>A (p.R4763Q) alteration is located in exon 77 (coding exon 76) of the SYNE1 gene. This alteration results from a G to A substitution at nucleotide position 14288, causing the arginine (R) at amino acid position 4763 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 4763 of the SYNE1 protein (p.Arg4763Gln). This variant is present in population databases (rs141883764, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 286148). 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
SYNE1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 07, 2023 | The SYNE1 c.14288G>A variant is predicted to result in the amino acid substitution p.Arg4763Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.084% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-152651319-C-T), which is more common than expected for a disease-causing variant. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at