3-57896582-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001377540.1(SLMAP):​c.1432G>C​(p.Asp478His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,607,756 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1432G>C	p.Asp478His	missense	Exon 16 of 25	NP_001364469.1	A0A590UJK3
	SLMAP	NM_001377538.1		c.1432G>C	p.Asp478His	missense	Exon 16 of 24	NP_001364467.1	A0A994J5K5
	SLMAP	NM_001377539.1		c.1432G>C	p.Asp478His	missense	Exon 16 of 24	NP_001364468.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.1432G>C	p.Asp478His	missense	Exon 16 of 25	ENSP00000499458.1	A0A590UJK3
	SLMAP	ENST00000417128.7	TSL:1	c.1318G>C	p.Asp440His	missense	Exon 14 of 23	ENSP00000412829.3	H7C3M8
	SLMAP	ENST00000449503.6	TSL:1	c.1267G>C	p.Asp423His	missense	Exon 12 of 20	ENSP00000412945.2	Q14BN4-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455690 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723932

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 43976

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: 0.00 AC: 0 AN: 1108830

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74282

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.15		Gain of glycosylation at S458 (P = 0.0054)
MVP		0.65
MPC		0.85
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.55
gMVP		0.50
Mutation Taster		=56/44	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;