chr6-152419598-C-A
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3
The NM_182961.4(SYNE1):c.5392G>T(p.Asp1798Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,612,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D1798H) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal recessive ataxia, Beauce typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- arthrogryposis multiplex congenita 3, myogenic typeInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Emery-Dreifuss muscular dystrophy 4, autosomal dominantInheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
- autosomal dominant Emery-Dreifuss muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal recessive myogenic arthrogryposis multiplex congenitaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.5392G>T | p.Asp1798Tyr | missense_variant | Exon 40 of 146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.5392G>T | p.Asp1798Tyr | missense_variant | Exon 40 of 146 | 1 | NM_182961.4 | ENSP00000356224.5 | ||
SYNE1 | ENST00000423061.6 | c.5413G>T | p.Asp1805Tyr | missense_variant | Exon 40 of 146 | 1 | ENSP00000396024.1 | |||
SYNE1 | ENST00000461872.6 | n.5610G>T | non_coding_transcript_exon_variant | Exon 38 of 55 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000398 AC: 6AN: 150912Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251312 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461732Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727166 show subpopulations
GnomAD4 genome AF: 0.0000398 AC: 6AN: 150912Hom.: 0 Cov.: 32 AF XY: 0.0000408 AC XY: 3AN XY: 73548 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
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. 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. ClinVar contains an entry for this variant (Variation ID: 586742). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1805 of the SYNE1 protein (p.Asp1805Tyr). This variant is present in population databases (rs772266857, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at