rs35219531
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001377540.1(SLMAP):c.1968T>A(p.Leu656=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,613,962 control chromosomes in the GnomAD database, including 677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 31 hom., cov: 32)
Exomes 𝑓: 0.026 ( 646 hom. )
Consequence
SLMAP
NM_001377540.1 synonymous
NM_001377540.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.277
Genes affected
SLMAP (HGNC:16643): (sarcolemma associated protein) This gene encodes a component of a conserved striatin-interacting phosphatase and kinase complex. Striatin family complexes participate in a variety of cellular processes including signaling, cell cycle control, cell migration, Golgi assembly, and apoptosis. The protein encoded by this gene is a coiled-coil, tail-anchored membrane protein with a single C-terminal transmembrane domain that is posttranslationally inserted into membranes. Mutations in this gene are associated with Brugada syndrome, a cardiac channelopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 3-57912649-T-A is Benign according to our data. Variant chr3-57912649-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 240722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-57912649-T-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.277 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0161 (2449/152298) while in subpopulation NFE AF= 0.0286 (1948/68018). AF 95% confidence interval is 0.0276. There are 31 homozygotes in gnomad4. There are 1092 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 2449 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLMAP | NM_001377540.1 | c.1968T>A | p.Leu656= | synonymous_variant | 20/25 | ENST00000671191.1 | |
LOC105377103 | XR_007095927.1 | n.364+4535A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLMAP | ENST00000671191.1 | c.1968T>A | p.Leu656= | synonymous_variant | 20/25 | NM_001377540.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0161 AC: 2449AN: 152180Hom.: 31 Cov.: 32
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GnomAD3 exomes AF: 0.0164 AC: 4115AN: 250368Hom.: 67 AF XY: 0.0168 AC XY: 2280AN XY: 135500
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GnomAD4 exome AF: 0.0264 AC: 38609AN: 1461664Hom.: 646 Cov.: 31 AF XY: 0.0256 AC XY: 18634AN XY: 727162
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 28, 2023 | - - |
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 08, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at