rs150439110
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001377540.1(SLMAP):c.2042A>G(p.Lys681Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,576,078 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_001377540.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLMAP | NM_001377540.1 | c.2042A>G | p.Lys681Arg | missense_variant | 21/25 | ENST00000671191.1 | |
LOC105377103 | XR_007095927.1 | n.364+4005T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLMAP | ENST00000671191.1 | c.2042A>G | p.Lys681Arg | missense_variant | 21/25 | NM_001377540.1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000228 AC: 57AN: 249910Hom.: 0 AF XY: 0.000244 AC XY: 33AN XY: 135132
GnomAD4 exome AF: 0.000398 AC: 566AN: 1423722Hom.: 0 Cov.: 26 AF XY: 0.000371 AC XY: 263AN XY: 709806
GnomAD4 genome AF: 0.000256 AC: 39AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74496
ClinVar
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 647 of the SLMAP protein (p.Lys647Arg). This variant is present in population databases (rs150439110, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of Brugada syndrome (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 411199). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at