rs35219531

Positions:

• chr3-57912649-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.277

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]

LOC105377103 (HGNC:):

ACMG classification

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	c.1968T>A	p.Leu656=	synonymous_variant	20/25	ENST00000671191.1	NP_001364469.1
LOC105377103	XR_007095927.1	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	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.: 31 Cov.: 32

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.: 67 AF XY: 0.0168 AC XY: 2280 AN XY: 135500

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.: 31 AF XY: 0.0256 AC XY: 18634 AN XY: 727162

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.: 31 Cov.: 32 AF XY: 0.0147 AC XY: 1092 AN XY: 74466

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.: 23

Bravo AF: 0.0158

Asia WGS AF: 0.00231 AC: 8 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

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

Other links and lift over

dbSNP: rs35219531; hg19: chr3-57898376; COSMIC: COSV55854724; COSMIC: COSV55854724;