Variant rs17058639 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001377540.1(SLMAP):c.1443C>T(p.Asp481=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

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

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/exons	MANE	Protein	UniProt
SLMAP	NM_001377540.1 linkuse as main transcript	c.1443C>T	p.Asp481=	splice_region_variant, synonymous_variant	17/25	ENST00000671191.1	NP_001364469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1 linkuse as main transcript	c.1443C>T	p.Asp481=	splice_region_variant, synonymous_variant	17/25		NM_001377540.1	ENSP00000499458	P4

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

GnomAD3 exomes

AF:

0.298

AC:

71962

AN:

241766

Hom.:

11645

AF XY:

0.299

AC XY:

39115

AN XY:

130630

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 SAS exome

AF:

0.342

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

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.346

Gnomad4 EAS exome

AF:

0.521

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.248

AC:

37744

AN:

151922

Hom.:

5194

Cov.:

AF XY:

0.257

AC XY:

19069

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.485

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.245

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.260

Hom.:

12860

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

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2017	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. -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.3

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0

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

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