chr6-152430143-G-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_182961.4(SYNE1):c.4757C>A(p.Thr1586Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00443 in 1,602,944 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1586A) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.4757C>A | p.Thr1586Lys | missense_variant | 36/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.4757C>A | p.Thr1586Lys | missense_variant | 36/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.4778C>A | p.Thr1593Lys | missense_variant | 36/146 | 1 | |||
SYNE1 | ENST00000461872.6 | n.4975C>A | non_coding_transcript_exon_variant | 34/55 | 1 | ||||
SYNE1 | ENST00000367253.8 | c.4757C>A | p.Thr1586Lys | missense_variant | 34/36 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00626 AC: 952AN: 152036Hom.: 19 Cov.: 33
GnomAD3 exomes AF: 0.0108 AC: 2573AN: 238176Hom.: 49 AF XY: 0.00897 AC XY: 1153AN XY: 128510
GnomAD4 exome AF: 0.00424 AC: 6152AN: 1450792Hom.: 148 Cov.: 30 AF XY: 0.00406 AC XY: 2931AN XY: 721104
GnomAD4 genome AF: 0.00627 AC: 954AN: 152152Hom.: 20 Cov.: 33 AF XY: 0.00759 AC XY: 565AN XY: 74396
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 14, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 12, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SYNE1: BP4, BS1, BS2 - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Autosomal recessive ataxia, Beauce type Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant;C5193121:Arthrogryposis multiplex congenita 3, myogenic type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 25, 2022 | - - |
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at