dbSNP rs774215191: SLMAP:p.Ser235Gly (chr3-57860714-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001377540.1(SLMAP):c.703A>G(p.Ser235Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,412,052 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

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLMAP
NM_001377540.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67

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]

SLMAP links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04751408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1 link	c.703A>G	p.Ser235Gly	missense_variant	Exon 9 of 25	ENST00000671191.1	NP_001364469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1 link	c.703A>G	p.Ser235Gly	missense_variant	Exon 9 of 25		NM_001377540.1	ENSP00000499458.1		A0A590UJK3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000476

AC:

AN:

209960

Hom.:

AF XY:

0.00000869

AC XY:

AN XY:

115090

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000989

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1412052

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

701794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brugada syndrome

Uncertain:1

Mar 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has not been reported in the literature in individuals with SLMAP-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces serine with glycine at codon 235 of the SLMAP protein (p.Ser235Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.18

.;.;.;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

.;D;D;D;D

M_CAP

Benign

0.0035

MetaRNN

Benign

0.048

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.065

N;N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.45

T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

0.0050

B;B;B;B;B

Vest4

0.14

MutPred

0.11

Gain of glycosylation at S235 (P = 0.0262);Gain of glycosylation at S235 (P = 0.0262);Gain of glycosylation at S235 (P = 0.0262);Gain of glycosylation at S235 (P = 0.0262);Gain of glycosylation at S235 (P = 0.0262);

MVP

0.35

MPC

0.18

ClinPred

0.25

GERP RS

2.9

Varity_R

0.072

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over