3-57860850-C-T

Variant names:

• chr3-57860850-C-T
• rs2306056
• NM_001377540.1:c.828+11C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001377538.1(SLMAP):​c.828+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 1,306,982 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SLMAP NM_001377538.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS2: High AC in GnomAdExome4 at 9 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377538.1. 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.828+11C>T		intron	N/A	NP_001364469.1
	SLMAP	NM_001377538.1		c.828+11C>T		intron	N/A	NP_001364467.1
	SLMAP	NM_001377539.1		c.828+11C>T		intron	N/A	NP_001364468.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.828+11C>T		intron	N/A	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.828+11C>T		intron	N/A	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.828+11C>T		intron	N/A	ENSP00000412945.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000689 AC: 9 AN: 1306982 Hom.: 0 Cov.: 28 AF XY: 0.00000308 AC XY: 2 AN XY: 649570

African (AFR) AF: 0.00 AC: 0 AN: 27746

American (AMR) AF: 0.0000349 AC: 1 AN: 28668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22484

East Asian (EAS) AF: 0.000168 AC: 6 AN: 35618

South Asian (SAS) AF: 0.00 AC: 0 AN: 70218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4596

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1015220

Other (OTH) AF: 0.00 AC: 0 AN: 53466

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 93

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.28
PhyloP100		-0.038
PromoterAI		-0.0066	Neutral

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: rs2306056; hg19: chr3-57846577;