3-57757730-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001377540.1(SLMAP):​c.79C>G​(p.Pro27Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLMAP
NM_001377540.1 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30529374).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLMAPNM_001377540.1 linkc.79C>G p.Pro27Ala missense_variant Exon 2 of 25 ENST00000671191.1 NP_001364469.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLMAPENST00000671191.1 linkc.79C>G p.Pro27Ala missense_variant Exon 2 of 25 NM_001377540.1 ENSP00000499458.1 A0A590UJK3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Brugada syndrome Uncertain:1
Sep 03, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 27 of the SLMAP protein (p.Pro27Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLMAP-related conditions. 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 disruptive. 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
.;.;.;D;.
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.96
.;D;D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.31
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.46
N;N;N;N;N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.1
D;D;D;D;D
REVEL
Benign
0.11
Sift
Benign
0.25
T;T;T;T;T
Sift4G
Benign
0.15
T;T;T;T;T
Polyphen
0.98
D;D;B;B;B
Vest4
0.64
MutPred
0.42
Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);
MVP
0.20
MPC
2.4
ClinPred
0.85
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.58
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-57743457; API