3-57896874-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001377540.1(SLMAP):c.1443C>T(p.Asp481Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,602,862 control chromosomes in the GnomAD database, including 59,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5194 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54164 hom. )

Consequence

SLMAP
NM_001377540.1 splice_region, synonymous

Scores

Splicing: ADA: 0.00003990

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.772

Publications

32 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.127).

BP6

Variant 3-57896874-C-T is Benign according to our data. Variant chr3-57896874-C-T is described in ClinVar as Benign. ClinVar VariationId is 516749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.772 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1 link	c.1443C>T	p.Asp481Asp	splice_region_variant, synonymous_variant	Exon 17 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.1443C>T	p.Asp481Asp	splice_region_variant, synonymous_variant	Exon 17 of 25		NM_001377540.1	ENSP00000499458.1

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37737

AN:

151806

Hom.:

5192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.277

GnomAD2 exomes

AF:

0.298

AC:

71962

AN:

241766

AF XY:

0.299

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.265

AC:

385207

AN:

1450940

Hom.:

54164

Cov.:

AF XY:

0.268

AC XY:

193508

AN XY:

721244

show subpopulations

African (AFR)

AF:

0.156

AC:

5136

AN:

32900

American (AMR)

AF:

0.358

AC:

15034

AN:

41954

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

8898

AN:

25742

East Asian (EAS)

AF:

0.521

AC:

20595

AN:

39530

South Asian (SAS)

AF:

0.342

AC:

28546

AN:

83348

European-Finnish (FIN)

AF:

0.291

AC:

15513

AN:

53308

Middle Eastern (MID)

AF:

0.336

AC:

1909

AN:

5688

European-Non Finnish (NFE)

AF:

0.246

AC:

272980

AN:

1108532

Other (OTH)

AF:

0.277

AC:

16596

AN:

59938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13458

26916

40373

53831

67289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9470

18940

28410

37880

47350

<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:

0.248

AC:

37744

AN:

151922

Hom.:

5194

Cov.:

AF XY:

0.257

AC XY:

19069

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.157

AC:

6517

AN:

41422

American (AMR)

AF:

0.327

AC:

4985

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1172

AN:

3468

East Asian (EAS)

AF:

0.485

AC:

2508

AN:

5166

South Asian (SAS)

AF:

0.370

AC:

1784

AN:

4818

European-Finnish (FIN)

AF:

0.302

AC:

3174

AN:

10524

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16652

AN:

67944

Other (OTH)

AF:

0.277

AC:

585

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1449

2898

4347

5796

7245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.257

Hom.:

23226

Bravo

AF:

0.246

Asia WGS

AF:

0.414

AC:

1437

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 04, 2023

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 28, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Brugada syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.3

(source)

DANN

Benign

0.68

PhyloP100

0.77

Mutation Taster

=75/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0

Splicevardb

2.0

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