rs973236515

Variant names:

• chr3-57757655-C-G
• NM_001377540.1:c.4C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-57757655-C-G
• chr3-57757655-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001377540.1(SLMAP):​c.4C>G​(p.Pro2Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P2S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.86

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4146525).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1	c.4C>G	p.Pro2Ala	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.4C>G	p.Pro2Ala	missense_variant	Exon 2 of 25		NM_001377540.1	ENSP00000499458.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461732 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727176

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;.;.;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	.;D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.34	N;N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0090	D;D;D;D;D
Sift4G	Uncertain	0.041	D;D;T;D;D
Polyphen		1.0	D;D;P;D;D
Vest4		0.64
MutPred		0.31		Loss of glycosylation at P2 (P = 0.0336);Loss of glycosylation at P2 (P = 0.0336);Loss of glycosylation at P2 (P = 0.0336);Loss of glycosylation at P2 (P = 0.0336);Loss of glycosylation at P2 (P = 0.0336);
MVP		0.34
MPC		2.6
ClinPred		0.77	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-57743382;