3-57757713-A-T

Variant names:

• chr3-57757713-A-T
• rs754847103
• NM_001377540.1:c.62A>T

Variant summary

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

The NM_001377540.1(SLMAP):​c.62A>T​(p.His21Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. H21R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.27
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1	c.62A>T	p.His21Leu	missense_variant	Exon 2 of 25	ENST00000671191.1	NP_001364469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1	c.62A>T	p.His21Leu	missense_variant	Exon 2 of 25		NM_001377540.1	ENSP00000499458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Uncertain	0.55	.;.;.;D;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;L;L
PhyloP100		9.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.6	D;D;D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.16	T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.95	P;P;B;D;P
Vest4		0.79
MutPred		0.34		Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);Gain of glycosylation at Y23 (P = 0.0041);
MVP		0.55
MPC		2.6
ClinPred		0.96	D
GERP RS		5.6
PromoterAI		-0.095	Neutral
Varity_R		0.54
gMVP		0.77
Mutation Taster		=10/90	disease causing

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: rs754847103; hg19: chr3-57743440;