6-152331249-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_182961.4(SYNE1):c.13436G>A(p.Arg4479His) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. R4479C) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.13436G>A | p.Arg4479His | missense_variant | 78/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.13436G>A | p.Arg4479His | missense_variant | 78/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.13223G>A | p.Arg4408His | missense_variant | 77/146 | 1 | |||
SYNE1 | ENST00000490135.6 | n.782G>A | non_coding_transcript_exon_variant | 2/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250280Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135238
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461822Hom.: 0 Cov.: 83 AF XY: 0.0000151 AC XY: 11AN XY: 727226
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 10, 2017 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4408 of the SYNE1 protein (p.Arg4408His). This variant is present in population databases (rs768085752, gnomAD 0.006%). 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: 448554). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 17, 2019 | - - |
SYNE1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 14, 2023 | The SYNE1 c.13223G>A variant is predicted to result in the amino acid substitution p.Arg4408His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-152652384-C-T). 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