rs149758819

Variant names:

• chr3-57849792-A-G
• rs149758819
• NM_001377540.1:c.495A>G
• SLMAP p.Leu165Leu

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001377540.1(SLMAP):​c.495A>G​(p.Leu165Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,573,820 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (10 hom.)
• Consequence: SLMAP NM_001377540.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.86
• Publications: 0 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, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-57849792-A-G is Benign according to our data. Variant chr3-57849792-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 240723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.
• BS2: High AC in GnomAd4 at 364 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377540.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	NM_001377540.1	MANE Select	c.495A>G	p.Leu165Leu	synonymous	Exon 6 of 25	NP_001364469.1	A0A590UJK3
	SLMAP	NM_001377538.1		c.495A>G	p.Leu165Leu	synonymous	Exon 6 of 24	NP_001364467.1	A0A994J5K5
	SLMAP	NM_001377539.1		c.495A>G	p.Leu165Leu	synonymous	Exon 6 of 24	NP_001364468.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.495A>G	p.Leu165Leu	synonymous	Exon 6 of 25	ENSP00000499458.1	A0A590UJK3
	SLMAP	ENST00000417128.7	TSL:1	c.495A>G	p.Leu165Leu	synonymous	Exon 6 of 23	ENSP00000412829.3	H7C3M8
	SLMAP	ENST00000449503.6	TSL:1	c.495A>G	p.Leu165Leu	synonymous	Exon 5 of 20	ENSP00000412945.2	Q14BN4-2

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00285 AC: 715 AN: 251168 AF XY: 0.00287

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00456

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00257 AC: 3647 AN: 1421482 Hom.: 10 Cov.: 24 AF XY: 0.00243 AC XY: 1725 AN XY: 709912

African (AFR) AF: 0.000581 AC: 19 AN: 32700

American (AMR) AF: 0.00148 AC: 66 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00471 AC: 122 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.000164 AC: 14 AN: 85358

European-Finnish (FIN) AF: 0.00902 AC: 481 AN: 53354

Middle Eastern (MID) AF: 0.000526 AC: 3 AN: 5702

European-Non Finnish (NFE) AF: 0.00261 AC: 2807 AN: 1075258

Other (OTH) AF: 0.00229 AC: 135 AN: 59030

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74502

African (AFR) AF: 0.000505 AC: 21 AN: 41578

American (AMR) AF: 0.000719 AC: 11 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00291 AC: 198 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00294 Hom.: 1

Bravo AF: 0.00181

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00320

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.45
CADD	Benign	7.1
DANN	Benign	0.80
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=293/7	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs149758819;

hg19: chr3-57835519;