3-57916912-G-C

Variant names:

• chr3-57916912-G-C
• NM_001377540.1:c.2145G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377540.1(SLMAP):​c.2145G>C​(p.Gln715His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q715Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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]

LOC105377103 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19138351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1	c.2145G>C	p.Gln715His	missense_variant	Exon 22 of 25	ENST00000671191.1	NP_001364469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1	c.2145G>C	p.Gln715His	missense_variant	Exon 22 of 25		NM_001377540.1	ENSP00000499458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Uncertain:1

Mar 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 681 of the SLMAP protein (p.Gln681His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLMAP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;.;T;.;T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	.;D;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.6	.;.;L;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Benign	0.21	T;T;T;T;D;D
Polyphen		1.0	D;D;D;D;.;D
Vest4		0.26
MutPred		0.10		.;.;Gain of glycosylation at S697 (P = 0.02);.;.;.;
MVP		0.58
MPC		0.64
ClinPred		0.83	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-57902639;