6-152367293-C-T
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_182961.4(SYNE1):c.9897G>A(p.Ala3299Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A3299A) has been classified as Likely benign.
Frequency
Consequence
NM_182961.4 synonymous
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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.9897G>A | p.Ala3299Ala | synonymous_variant | Exon 62 of 146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000358 AC: 9AN: 251482 AF XY: 0.0000515 show subpopulations
GnomAD4 exome AF: 0.000101 AC: 147AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 727244 show subpopulations
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74326 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
SYNE1: BP4, BP7 -
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Autosomal recessive ataxia, Beauce type Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at