3-57928451-T-C

Variant names:

• chr3-57928451-T-C
• rs1043045
• NM_001377540.1:c.*1162T>C

Variant summary

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

The ENST00000671191.1(SLMAP):​c.*1162T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,930 control chromosomes in the GnomAD database, including 7,672 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 0.31 (7672 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLMAP ENST00000671191.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 10 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000671191.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	NM_001377540.1	MANE Select	c.*1162T>C		3_prime_UTR	Exon 25 of 25	NP_001364469.1
	SLMAP	NR_165328.1		n.4735T>C		non_coding_transcript_exon	Exon 23 of 23
	SLMAP	NM_001377538.1		c.*1063T>C		3_prime_UTR	Exon 24 of 24	NP_001364467.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.*1162T>C		3_prime_UTR	Exon 25 of 25	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.*1162T>C		3_prime_UTR	Exon 23 of 23	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.*1063T>C		3_prime_UTR	Exon 20 of 20	ENSP00000412945.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47180 AN: 151812 Hom.: 7659 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.324

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.311 AC: 47229 AN: 151930 Hom.: 7672 Cov.: 32 AF XY: 0.317 AC XY: 23557 AN XY: 74240

African (AFR) AF: 0.370 AC: 15341 AN: 41422

American (AMR) AF: 0.350 AC: 5335 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2464 AN: 5160

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4816

European-Finnish (FIN) AF: 0.301 AC: 3181 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16812 AN: 67940

Other (OTH) AF: 0.323 AC: 680 AN: 2106

Alfa AF: 0.268 Hom.: 7204

Bravo AF: 0.317

Asia WGS AF: 0.425 AC: 1482 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		2.4
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: rs1043045; hg19: chr3-57914178;