chr3-57890051-C-T

Variant names:

• chr3-57890051-C-T
• rs369261823
• NM_001377540.1:c.1311C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001304422.3(SLMAP):​c.-139C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,612,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: SLMAP NM_001304422.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.073).
• BP6: Variant 3-57890051-C-T is Benign according to our data. Variant chr3-57890051-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 532155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 22 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304422.3. 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.1311C>T	p.Ile437Ile	synonymous	Exon 15 of 25	NP_001364469.1	A0A590UJK3
	SLMAP	NM_001304422.3		c.-139C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001291351.1	B7Z964
	SLMAP	NM_001311178.2		c.-139C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001298107.1	Q14BN4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.1311C>T	p.Ile437Ile	synonymous	Exon 15 of 25	ENSP00000499458.1	A0A590UJK3
	SLMAP	ENST00000417128.7	TSL:1	c.1197C>T	p.Ile399Ile	synonymous	Exon 13 of 23	ENSP00000412829.3	H7C3M8
	SLMAP	ENST00000449503.6	TSL:1	c.1146C>T	p.Ile382Ile	synonymous	Exon 11 of 20	ENSP00000412945.2	Q14BN4-2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251318 AF XY: 0.000140

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000320 AC: 468 AN: 1460284 Hom.: 0 Cov.: 29 AF XY: 0.000311 AC XY: 226 AN XY: 726540

African (AFR) AF: 0.000179 AC: 6 AN: 33460

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86212

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000402 AC: 447 AN: 1110574

Other (OTH) AF: 0.0000995 AC: 6 AN: 60330

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74318

African (AFR) AF: 0.0000724 AC: 3 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000262 Hom.: 0

Bravo AF: 0.000144

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Brugada syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		1.1
PromoterAI		-0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs369261823; hg19: chr3-57875778;