rs138691290
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_182961.4(SYNE1):c.4735A>G(p.Ile1579Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,605,648 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.4735A>G | p.Ile1579Val | missense_variant | 36/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.4735A>G | p.Ile1579Val | missense_variant | 36/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.4756A>G | p.Ile1586Val | missense_variant | 36/146 | 1 | |||
SYNE1 | ENST00000461872.6 | n.4953A>G | non_coding_transcript_exon_variant | 34/55 | 1 | ||||
SYNE1 | ENST00000367253.8 | c.4735A>G | p.Ile1579Val | missense_variant | 34/36 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000792 AC: 19AN: 239996Hom.: 0 AF XY: 0.0000695 AC XY: 9AN XY: 129486
GnomAD4 exome AF: 0.0000427 AC: 62AN: 1453370Hom.: 0 Cov.: 31 AF XY: 0.0000388 AC XY: 28AN XY: 722460
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 05, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 03, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 13, 2018 | - - |
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 variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is present in population databases (rs138691290, gnomAD 0.02%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1586 of the SYNE1 protein (p.Ile1586Val). ClinVar contains an entry for this variant (Variation ID: 580292). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at