rs148212715
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS2_Supporting
The NM_182961.4(SYNE1):āc.10784A>Gā(p.Asn3595Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,614,218 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. N3595N) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.10784A>G | p.Asn3595Ser | missense_variant | 67/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.10784A>G | p.Asn3595Ser | missense_variant | 67/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.10805A>G | p.Asn3602Ser | missense_variant | 67/146 | 1 | |||
SYNE1 | ENST00000471834.1 | n.3922A>G | non_coding_transcript_exon_variant | 10/19 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000171 AC: 43AN: 251466Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135902
GnomAD4 exome AF: 0.000320 AC: 468AN: 1461894Hom.: 1 Cov.: 33 AF XY: 0.000322 AC XY: 234AN XY: 727248
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 14, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 08, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 27, 2019 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3602 of the SYNE1 protein (p.Asn3602Ser). This variant is present in population databases (rs148212715, gnomAD 0.03%). This missense change has been observed in individual(s) with cerebellar ataxia, congenital cerebellar hypoplasia, and cognitive impairment (PMID: 30275942). ClinVar contains an entry for this variant (Variation ID: 285321). 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 serine 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at