rs6768930

Variant names:

• chr3-57794109-T-C
• rs6768930
• NM_001377540.1:c.198+36260T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-57794109-T-C
• chr3-57794109-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377540.1(SLMAP):​c.198+36260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,002 control chromosomes in the GnomAD database, including 11,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11076 hom., cov: 31)
• Consequence: SLMAP NM_001377540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1	c.198+36260T>C		intron_variant	Intron 2 of 24	ENST00000671191.1	NP_001364469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1	c.198+36260T>C		intron_variant	Intron 2 of 24		NM_001377540.1	ENSP00000499458.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55331 AN: 151882 Hom.: 11086 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55329 AN: 152002 Hom.: 11076 Cov.: 31 AF XY: 0.371 AC XY: 27558 AN XY: 74266

African (AFR) AF: 0.194 AC: 8064 AN: 41480

American (AMR) AF: 0.417 AC: 6364 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1628 AN: 3466

East Asian (EAS) AF: 0.554 AC: 2856 AN: 5154

South Asian (SAS) AF: 0.595 AC: 2869 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4436 AN: 10548

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27655 AN: 67946

Other (OTH) AF: 0.391 AC: 825 AN: 2110

Alfa AF: 0.380 Hom.: 15816

Bravo AF: 0.352

Asia WGS AF: 0.558 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs6768930; hg19: chr3-57779836;