rs1016820088

Variant names:

• chr3-57896582-G-A
• rs1016820088
• NM_001377540.1:c.1432G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-57896582-G-A
• chr3-57896582-G-C
• chr3-57896582-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001377540.1(SLMAP):​c.1432G>A​(p.Asp478Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D478Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31186828).
• BS2: High AC in GnomAdExome4 at 6 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.1432G>A	p.Asp478Asn	missense	Exon 16 of 25	NP_001364469.1
	SLMAP	NM_001377538.1		c.1432G>A	p.Asp478Asn	missense	Exon 16 of 24	NP_001364467.1
	SLMAP	NM_001377539.1		c.1432G>A	p.Asp478Asn	missense	Exon 16 of 24	NP_001364468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.1432G>A	p.Asp478Asn	missense	Exon 16 of 25	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.1318G>A	p.Asp440Asn	missense	Exon 14 of 23	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.1267G>A	p.Asp423Asn	missense	Exon 12 of 20	ENSP00000412945.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 243336 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000412 AC: 6 AN: 1455688 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723932

African (AFR) AF: 0.0000301 AC: 1 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25832

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108830

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Brugada syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.13		Gain of glycosylation at S458 (P = 0.0054)
MVP		0.79
MPC		0.77
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.42
gMVP		0.40
Mutation Taster		=77/23	polymorphism

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: rs1016820088; hg19: chr3-57882309; COSMIC: COSV108097149;