NM_001377540.1:c.1317A>G

Variant names:

• chr3-57890057-A-G
• rs189861519
• NM_001377540.1:c.1317A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The NM_001377540.1(SLMAP):​c.1317A>G​(p.Glu439Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: SLMAP NM_001377540.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.47
• 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, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP6: Variant 3-57890057-A-G is Benign according to our data. Variant chr3-57890057-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.47 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	NM_001377540.1	MANE Select	c.1317A>G	p.Glu439Glu	synonymous	Exon 15 of 25	NP_001364469.1
	SLMAP	NM_001377538.1		c.1317A>G	p.Glu439Glu	synonymous	Exon 15 of 24	NP_001364467.1
	SLMAP	NM_001377539.1		c.1317A>G	p.Glu439Glu	synonymous	Exon 15 of 24	NP_001364468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.1317A>G	p.Glu439Glu	synonymous	Exon 15 of 25	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.1203A>G	p.Glu401Glu	synonymous	Exon 13 of 23	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.1152A>G	p.Glu384Glu	synonymous	Exon 11 of 20	ENSP00000412945.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000298 AC: 75 AN: 251354 AF XY: 0.000258

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461280 Hom.: 0 Cov.: 29 AF XY: 0.0000564 AC XY: 41 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00188 AC: 84 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111462

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.000327 AC: 5 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000907

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Brugada syndrome (1)
-	-	1	not specified (1)
-	-	1	SLMAP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.56
PhyloP100		1.5
PromoterAI		-0.095	Neutral

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

Other links and lift over

dbSNP: rs189861519; hg19: chr3-57875784;