chr6-152215033-C-T
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_182961.4(SYNE1):c.22219G>A(p.Ala7407Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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
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: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.22219G>A | p.Ala7407Thr | missense_variant | Exon 122 of 146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152164Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000279 AC: 7AN: 251284 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.0000743 AC XY: 54AN XY: 727200 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74330 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:3
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not specified Uncertain:1
Variant summary: SYNE1 c.22006G>A (p.Ala7336Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251284 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.22006G>A in individuals affected with Autosomal recessive ataxia, Beauce type and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 284477). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at