rs2306056

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-57860850-C-A
• chr3-57860850-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377538.1(SLMAP):​c.828+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,447,716 control chromosomes in the GnomAD database, including 19,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3032 hom., cov: 31)
  • Exomes 𝑓: 0.19 (16741 hom.)
• Consequence: SLMAP NM_001377538.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-57860850-C-A is Benign according to our data. Variant chr3-57860850-C-A is described in ClinVar as Benign. ClinVar VariationId is 260135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

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>A		intron	N/A	NP_001364469.1
	SLMAP	NM_001377538.1		c.828+11C>A		intron	N/A	NP_001364467.1
	SLMAP	NM_001377539.1		c.828+11C>A		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>A		intron	N/A	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.828+11C>A		intron	N/A	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.828+11C>A		intron	N/A	ENSP00000412945.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29582 AN: 147764 Hom.: 3031 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.261 AC: 37806 AN: 144904 AF XY: 0.257

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.451

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.193 AC: 251013 AN: 1299842 Hom.: 16741 Cov.: 28 AF XY: 0.192 AC XY: 123911 AN XY: 646156

African (AFR) AF: 0.173 AC: 4765 AN: 27572

American (AMR) AF: 0.280 AC: 7967 AN: 28412

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4127 AN: 22398

East Asian (EAS) AF: 0.377 AC: 13337 AN: 35358

South Asian (SAS) AF: 0.132 AC: 9209 AN: 69918

European-Finnish (FIN) AF: 0.173 AC: 8452 AN: 48848

Middle Eastern (MID) AF: 0.161 AC: 737 AN: 4578

European-Non Finnish (NFE) AF: 0.190 AC: 191979 AN: 1009570

Other (OTH) AF: 0.196 AC: 10440 AN: 53188

GnomAD4 genome AF: 0.200 AC: 29609 AN: 147874 Hom.: 3032 Cov.: 31 AF XY: 0.201 AC XY: 14425 AN XY: 71906

African (AFR) AF: 0.182 AC: 7343 AN: 40354

American (AMR) AF: 0.243 AC: 3625 AN: 14896

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 663 AN: 3426

East Asian (EAS) AF: 0.436 AC: 2234 AN: 5120

South Asian (SAS) AF: 0.132 AC: 614 AN: 4654

European-Finnish (FIN) AF: 0.185 AC: 1758 AN: 9504

Middle Eastern (MID) AF: 0.176 AC: 49 AN: 278

European-Non Finnish (NFE) AF: 0.191 AC: 12754 AN: 66698

Other (OTH) AF: 0.214 AC: 437 AN: 2044

Alfa AF: 0.0399 Hom.: 93

Bravo AF: 0.207

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Brugada syndrome (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.31
PhyloP100		-0.038
PromoterAI		-0.014	Neutral
Mutation Taster		=7/93	disease causing

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

Other links and lift over

dbSNP: rs2306056; hg19: chr3-57846577;