rs17745496

Positions:

• chr3-57916912-G-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.2145G>A​(p.Gln715=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,330 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (65 hom., cov: 32)
  • Exomes 𝑓: 0.028 (645 hom.)
• Consequence: SLMAP NM_001377540.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.20

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=-0.48).
• BP6: Variant 3-57916912-G-A is Benign according to our data. Variant chr3-57916912-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-57916912-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0233 (3543/152132) while in subpopulation NFE AF= 0.0342 (2326/68014). AF 95% confidence interval is 0.033. There are 65 homozygotes in gnomad4. There are 1662 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLMAP	NM_001377540.1	c.2145G>A	p.Gln715=	synonymous_variant	22/25	ENST00000671191.1	NP_001364469.1
LOC105377103	XR_007095927.1	n.364+272C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1	c.2145G>A	p.Gln715=	synonymous_variant	22/25		NM_001377540.1	ENSP00000499458	P4

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3543 AN: 152014 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0317

GnomAD3 exomes AF: 0.0238 AC: 5974 AN: 250662 Hom.: 102 AF XY: 0.0244 AC XY: 3306 AN XY: 135444

Gnomad AFR exome AF: 0.00437

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0485

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0123

Gnomad FIN exome AF: 0.0241

Gnomad NFE exome AF: 0.0328

Gnomad OTH exome AF: 0.0272

GnomAD4 exome AF: 0.0277 AC: 40445 AN: 1460198 Hom.: 645 Cov.: 30 AF XY: 0.0273 AC XY: 19859 AN XY: 726178

Gnomad4 AFR exome AF: 0.00413

Gnomad4 AMR exome AF: 0.0195

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.0251

Gnomad4 NFE exome AF: 0.0307

Gnomad4 OTH exome AF: 0.0249

GnomAD4 genome AF: 0.0233 AC: 3543 AN: 152132 Hom.: 65 Cov.: 32 AF XY: 0.0223 AC XY: 1662 AN XY: 74378

Gnomad4 AFR AF: 0.00448

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.0325 Hom.: 120

Bravo AF: 0.0236

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0367

EpiControl AF: 0.0359

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Jul 29, 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	-0.48
CADD	Benign	5.8
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17745496; hg19: chr3-57902639;