Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2

The NM_001377540.1(SLMAP):c.2145G>A(p.Gln715Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,330 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 65 hom., cov: 32)

Exomes 𝑓: 0.028 ( 645 hom. )

Consequence

SLMAP
NM_001377540.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.20

Publications

5 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.24).

BP6

Variant 3-57916912-G-A is Benign according to our data. Variant chr3-57916912-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0233 (3543/152132) while in subpopulation NFE AF = 0.0342 (2326/68014). AF 95% confidence interval is 0.033. There are 65 homozygotes in GnomAd4. There are 1662 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3543 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377540.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLMAP	NM_001377540.1	MANE Select	c.2145G>A	p.Gln715Gln	synonymous	Exon 22 of 25	NP_001364469.1
SLMAP	NM_001377538.1		c.2166G>A	p.Gln722Gln	synonymous	Exon 22 of 24	NP_001364467.1
SLMAP	NM_001377539.1		c.2145G>A	p.Gln715Gln	synonymous	Exon 22 of 24	NP_001364468.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLMAP	ENST00000671191.1	MANE Select	c.2145G>A	p.Gln715Gln	synonymous	Exon 22 of 25	ENSP00000499458.1
SLMAP	ENST00000417128.7	TSL:1	c.2031G>A	p.Gln677Gln	synonymous	Exon 20 of 23	ENSP00000412829.3
SLMAP	ENST00000449503.6	TSL:1	c.1980G>A	p.Gln660Gln	synonymous	Exon 18 of 20	ENSP00000412945.2

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3543

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00892

Gnomad FIN

AF:

0.0242

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0317

GnomAD2 exomes

AF:

0.0238

AC:

5974

AN:

250662

AF XY:

0.0244

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.0485

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0241

Gnomad NFE exome

AF:

0.0328

Gnomad OTH exome

AF:

0.0272

GnomAD4 exome

AF:

0.0277

AC:

40445

AN:

1460198

Hom.:

645

Cov.:

AF XY:

0.0273

AC XY:

19859

AN XY:

726178

show subpopulations

African (AFR)

AF:

0.00413

AC:

138

AN:

33406

American (AMR)

AF:

0.0195

AC:

870

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1272

AN:

26100

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39614

South Asian (SAS)

AF:

0.0126

AC:

1083

AN:

86182

European-Finnish (FIN)

AF:

0.0251

AC:

1339

AN:

53414

Middle Eastern (MID)

AF:

0.0266

AC:

153

AN:

5760

European-Non Finnish (NFE)

AF:

0.0307

AC:

34087

AN:

1110720

Other (OTH)

AF:

0.0249

AC:

1500

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1785

3570

5356

7141

8926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1214

2428

3642

4856

6070

<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:

0.0233

AC:

3543

AN:

152132

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1662

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00448

AC:

186

AN:

41522

American (AMR)

AF:

0.0297

AC:

454

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0528

AC:

183

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00934

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0242

AC:

256

AN:

10558

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0342

AC:

2326

AN:

68014

Other (OTH)

AF:

0.0314

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

184

369

553

738

922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0317

Hom.:

154

Bravo

AF:

0.0236

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0367

EpiControl

AF:

0.0359

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Brugada syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.8

(source)

DANN

Benign

0.66

PhyloP100

2.2

PromoterAI

-0.0076

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs17745496

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over