rs111294347

Variant names:

• chr3-57871712-A-G
• rs111294347
• NM_001377540.1:c.1300+14A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001377538.1(SLMAP):​c.1300+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,586,108 control chromosomes in the GnomAD database, including 2,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (97 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1946 hom.)
• Consequence: SLMAP NM_001377538.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.81
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Brugada syndrome

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 3-57871712-A-G is Benign according to our data. Variant chr3-57871712-A-G is described in ClinVar as Benign. ClinVar VariationId is 260134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377538.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	NM_001377540.1	MANE Select	c.1300+14A>G		intron	N/A	NP_001364469.1
	SLMAP	NM_001377538.1		c.1300+14A>G		intron	N/A	NP_001364467.1
	SLMAP	NM_001377539.1		c.1300+14A>G		intron	N/A	NP_001364468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.1300+14A>G		intron	N/A	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.1186+6855A>G		intron	N/A	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.1135+6996A>G		intron	N/A	ENSP00000412945.2

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4625 AN: 152076 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0312

GnomAD2 exomes AF: 0.0326 AC: 7981 AN: 244670 AF XY: 0.0335

Gnomad AFR exome AF: 0.00865

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0202

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0525

Gnomad OTH exome AF: 0.0416

GnomAD4 exome AF: 0.0474 AC: 67906 AN: 1433914 Hom.: 1946 Cov.: 25 AF XY: 0.0464 AC XY: 33146 AN XY: 714964

African (AFR) AF: 0.00736 AC: 242 AN: 32902

American (AMR) AF: 0.0189 AC: 837 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 510 AN: 25894

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39404

South Asian (SAS) AF: 0.0180 AC: 1529 AN: 85016

European-Finnish (FIN) AF: 0.0202 AC: 1080 AN: 53382

Middle Eastern (MID) AF: 0.0389 AC: 216 AN: 5552

European-Non Finnish (NFE) AF: 0.0560 AC: 60944 AN: 1088088

Other (OTH) AF: 0.0428 AC: 2544 AN: 59420

GnomAD4 genome AF: 0.0304 AC: 4626 AN: 152194 Hom.: 97 Cov.: 32 AF XY: 0.0287 AC XY: 2138 AN XY: 74398

African (AFR) AF: 0.0101 AC: 421 AN: 41538

American (AMR) AF: 0.0266 AC: 405 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4828

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0503 AC: 3420 AN: 68008

Other (OTH) AF: 0.0313 AC: 66 AN: 2108

Alfa AF: 0.0426 Hom.: 257

Bravo AF: 0.0303

Asia WGS AF: 0.00693 AC: 24 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Brugada syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs111294347; hg19: chr3-57857439;