Variant 3-57912649-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001377540.1(SLMAP):c.1968T>A(p.Leu656=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,613,962 control chromosomes in the GnomAD database, including 677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 31 hom., cov: 32)

Exomes 𝑓: 0.026 ( 646 hom. )

Consequence

SLMAP
NM_001377540.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.277

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 3-57912649-T-A is Benign according to our data. Variant chr3-57912649-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 240722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-57912649-T-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.277 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0161 (2449/152298) while in subpopulation NFE AF= 0.0286 (1948/68018). AF 95% confidence interval is 0.0276. There are 31 homozygotes in gnomad4. There are 1092 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2449 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLMAP	NM_001377540.1 linkuse as main transcript	c.1968T>A	p.Leu656=	synonymous_variant	20/25	ENST00000671191.1	NP_001364469.1
LOC105377103	XR_007095927.1 linkuse as main transcript	n.364+4535A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1 linkuse as main transcript	c.1968T>A	p.Leu656=	synonymous_variant	20/25		NM_001377540.1	ENSP00000499458	P4

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2449

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00923

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0164

AC:

4115

AN:

250368

Hom.:

AF XY:

0.0168

AC XY:

2280

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.00408

Gnomad AMR exome

AF:

0.00634

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00582

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0264

AC:

38609

AN:

1461664

Hom.:

646

Cov.:

AF XY:

0.0256

AC XY:

18634

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00358

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.00390

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00562

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.0321

Gnomad4 OTH exome

AF:

0.0216

GnomAD4 genome

AF:

0.0161

AC:

2449

AN:

152298

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1092

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00923

Gnomad4 NFE

AF:

0.0286

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0257

EpiControl

AF:

0.0289

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

May 28, 2023

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.7

DANN

Benign

0.74

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