rs35029175

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001377540.1(SLMAP):c.1991A>G(p.Gln664Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00113 in 1,612,582 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q664H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

SLMAP
NM_001377540.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.26

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Brugada syndrome
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, Orphanet, ClinGen

SLMAP links:

LOC105377103 (HGNC:):

LOC105377103 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03937456).

BP6

Variant 3-57912672-A-G is Benign according to our data. Variant chr3-57912672-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 463277.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 95 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1 link	c.1991A>G	p.Gln664Arg	missense_variant	Exon 20 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.1991A>G	p.Gln664Arg	missense_variant	Exon 20 of 25		NM_001377540.1	ENSP00000499458.1		A0A590UJK3

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000549

AC:

137

AN:

249686

AF XY:

0.000547

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.00118

AC:

1729

AN:

1460216

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

789

AN XY:

726114

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33436

American (AMR)

AF:

0.000112

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00152

AC:

1688

AN:

1110738

Other (OTH)

AF:

0.000481

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000623

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41594

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

68026

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000961

Hom.:

Bravo

AF:

0.000552

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brugada syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;.;T;.;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;D;D;D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.039

T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.9

.;.;M;.;.;.

PhyloP100

4.3

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0080

D;D;D;D;T;D

Sift4G

Benign

0.56

T;T;T;T;T;T

Polyphen

1.0

D;D;D;D;.;D

Vest4

0.26

MVP

0.57

MPC

0.39

ClinPred

0.026

GERP RS

5.3

Varity_R

0.31

gMVP

0.17

Mutation Taster

=65/35

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over