rs143689400

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001377540.1(SLMAP):c.2272A>T(p.Ser758Cys) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,613,986 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 4 hom. )

Consequence

SLMAP
NM_001377540.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.52

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:

LOC105377103 (HGNC:):

LOC105377103 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023350477).

BP6

Variant 3-57917039-A-T is Benign according to our data. Variant chr3-57917039-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 416638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-57917039-A-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLMAP	NM_001377540.1 linkuse as main transcript	c.2272A>T	p.Ser758Cys	missense_variant	22/25	ENST00000671191.1
LOC105377103	XR_007095927.1 linkuse as main transcript	n.364+145T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLMAP	ENST00000671191.1 linkuse as main transcript	c.2272A>T	p.Ser758Cys	missense_variant	22/25		NM_001377540.1	P4

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00104

AC:

261

AN:

251074

Hom.:

AF XY:

0.00107

AC XY:

145

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00208

AC:

3041

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

1496

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000707

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152322

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00143

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000865

AC:

105

EpiCase

AF:

0.00229

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Apr 10, 2023

- -

Brugada syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.027

MetaRNN

Benign

0.023

T;T;T;T;T;T

MetaSVM

Uncertain

-0.16

MutationTaster

Benign

0.60

D;D;D;D;N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.010

D;D;D;D;D;D

Sift4G

Benign

0.088

T;T;T;T;D;D

Polyphen

0.99

D;D;P;D;.;P

Vest4

0.16

MVP

0.37

MPC

0.44

ClinPred

0.026

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.10

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

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