rs150335599
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_StrongBP6BS2_Supporting
The NM_182961.4(SYNE1):c.18662C>T(p.Thr6221Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000867 in 1,614,026 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T6221S) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.18662C>T | p.Thr6221Ile | missense_variant | 99/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.18662C>T | p.Thr6221Ile | missense_variant | 99/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.18449C>T | p.Thr6150Ile | missense_variant | 98/146 | 1 | |||
SYNE1 | ENST00000367256.9 | n.2354C>T | non_coding_transcript_exon_variant | 14/61 | 1 | ||||
SYNE1 | ENST00000409694.6 | n.2246C>T | non_coding_transcript_exon_variant | 12/59 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000207 AC: 52AN: 251468Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135916
GnomAD4 exome AF: 0.0000882 AC: 129AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000963 AC XY: 70AN XY: 727246
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74322
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 28, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 31, 2016 | - - |
Autosomal recessive ataxia, Beauce type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | - - |
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at