rs17058639

Variant names:

• chr3-57896874-C-T
• rs17058639
• NM_001377540.1:c.1443C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001304422.3(SLMAP):​c.-7C>T variant causes a 5 prime UTR premature start codon gain 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. 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_001304422.3 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.00003990
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.772

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 -18 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].
• 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	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	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.: 32

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

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.: 32 AF XY: 0.268 AC XY: 193508 AN XY: 721244

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.: 32 AF XY: 0.257 AC XY: 19069 AN XY: 74244

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

Submissions by phenotype

not specified Benign:2

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. -

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

- -

Brugada syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Other links and lift over

dbSNP: rs17058639; hg19: chr3-57882601; COSMIC: COSV55844439; COSMIC: COSV55844439;