3-57757519-G-A

Variant names:

• chr3-57757519-G-A
• rs1053711
• NM_001377540.1:c.-133G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001377540.1(SLMAP):​c.-133G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 758,774 control chromosomes in the GnomAD database, including 29,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4643 hom., cov: 32)
  • Exomes 𝑓: 0.27 (24773 hom.)
• Consequence: SLMAP NM_001377540.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.38
• Publications: 14 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 3-57757519-G-A is Benign according to our data. Variant chr3-57757519-G-A is described in ClinVar as [Benign]. Clinvar id is 1262629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1	c.-133G>A		5_prime_UTR_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.-133G>A		5_prime_UTR_variant	Exon 2 of 25		NM_001377540.1	ENSP00000499458.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32927 AN: 152010 Hom.: 4643 Cov.: 32

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.270 AC: 163592 AN: 606644 Hom.: 24773 Cov.: 8 AF XY: 0.270 AC XY: 85946 AN XY: 318570

African (AFR) AF: 0.0502 AC: 839 AN: 16706

American (AMR) AF: 0.144 AC: 4463 AN: 30918

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 4771 AN: 16984

East Asian (EAS) AF: 0.0180 AC: 580 AN: 32190

South Asian (SAS) AF: 0.226 AC: 12462 AN: 55152

European-Finnish (FIN) AF: 0.324 AC: 11527 AN: 35546

Middle Eastern (MID) AF: 0.289 AC: 699 AN: 2422

European-Non Finnish (NFE) AF: 0.312 AC: 120027 AN: 384822

Other (OTH) AF: 0.258 AC: 8224 AN: 31904

GnomAD4 genome AF: 0.216 AC: 32933 AN: 152130 Hom.: 4643 Cov.: 32 AF XY: 0.215 AC XY: 15956 AN XY: 74338

African (AFR) AF: 0.0534 AC: 2221 AN: 41562

American (AMR) AF: 0.208 AC: 3173 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3468

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5166

South Asian (SAS) AF: 0.202 AC: 972 AN: 4822

European-Finnish (FIN) AF: 0.320 AC: 3373 AN: 10554

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21343 AN: 67968

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.278 Hom.: 25711

Bravo AF: 0.197

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 04, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		3.4
PromoterAI		-0.038	Neutral
Mutation Taster		=299/1	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: rs1053711; hg19: chr3-57743246;