rs2306056

chr3-57860850-C-Achr3-57860850-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377540.1(SLMAP):c.828+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,447,716 control chromosomes in the GnomAD database, including 19,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3032 hom., cov: 31)
  • Exomes 𝑓: 0.19 (16741 hom.)
• Consequence: SLMAP NM_001377540.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0380

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-57860850-C-A is Benign according to our data. Variant chr3-57860850-C-A is described in ClinVar as [Benign]. Clinvar id is 260135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-57860850-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLMAP	NM_001377540.1	c.828+11C>A		intron_variant		ENST00000671191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLMAP	ENST00000671191.1	c.828+11C>A		intron_variant			NM_001377540.1	P4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29582 AN: 147764 Hom.: 3031 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.261 AC: 37806 AN: 144904 Hom.: 2109 AF XY: 0.257 AC XY: 20244 AN XY: 78742

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.451

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.193 AC: 251013 AN: 1299842 Hom.: 16741 Cov.: 28 AF XY: 0.192 AC XY: 123911 AN XY: 646156

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.200 AC: 29609 AN: 147874 Hom.: 3032 Cov.: 31 AF XY: 0.201 AC XY: 14425 AN XY: 71906

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.214

Alfa AF: 0.0399 Hom.: 93

Bravo AF: 0.207

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Brugada syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Phosphorus, Inc.	Aug 01, 2017	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.2
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2306056; hg19: chr3-57846577;