chr3-57896874-C-T

Variant names:

• chr3-57896874-C-T
• rs17058639
• NM_001377540.1:c.1443C>T

Variant summary

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

The NM_001304422.3(SLMAP):​c.-7C>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 0.264 in 1,602,862 control chromosomes in the GnomAD database, including 59,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5194 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54164 hom.)
• Consequence: SLMAP NM_001304422.3 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.00003990
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.772
• Publications: 32 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 (REVEL=0.127).
• BP6: Variant 3-57896874-C-T is Benign according to our data. Variant chr3-57896874-C-T is described in ClinVar as Benign. ClinVar VariationId is 516749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

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.1443C>T	p.Asp481Asp	splice_region synonymous	Exon 17 of 25	NP_001364469.1	A0A590UJK3
	SLMAP	NM_001304422.3		c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	NP_001291351.1	B7Z964
	SLMAP	NM_001311178.2		c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 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.1443C>T	p.Asp481Asp	splice_region synonymous	Exon 17 of 25	ENSP00000499458.1	A0A590UJK3
	SLMAP	ENST00000417128.7	TSL:1	c.1329C>T	p.Asp443Asp	splice_region synonymous	Exon 15 of 23	ENSP00000412829.3	H7C3M8
	SLMAP	ENST00000449503.6	TSL:1	c.1278C>T	p.Asp426Asp	splice_region synonymous	Exon 13 of 20	ENSP00000412945.2	Q14BN4-2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37737 AN: 151806 Hom.: 5192 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.277

GnomAD2 exomes AF: 0.298 AC: 71962 AN: 241766 AF XY: 0.299

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.265 AC: 385207 AN: 1450940 Hom.: 54164 Cov.: 32 AF XY: 0.268 AC XY: 193508 AN XY: 721244

African (AFR) AF: 0.156 AC: 5136 AN: 32900

American (AMR) AF: 0.358 AC: 15034 AN: 41954

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 8898 AN: 25742

East Asian (EAS) AF: 0.521 AC: 20595 AN: 39530

South Asian (SAS) AF: 0.342 AC: 28546 AN: 83348

European-Finnish (FIN) AF: 0.291 AC: 15513 AN: 53308

Middle Eastern (MID) AF: 0.336 AC: 1909 AN: 5688

European-Non Finnish (NFE) AF: 0.246 AC: 272980 AN: 1108532

Other (OTH) AF: 0.277 AC: 16596 AN: 59938

GnomAD4 genome AF: 0.248 AC: 37744 AN: 151922 Hom.: 5194 Cov.: 32 AF XY: 0.257 AC XY: 19069 AN XY: 74244

African (AFR) AF: 0.157 AC: 6517 AN: 41422

American (AMR) AF: 0.327 AC: 4985 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2508 AN: 5166

South Asian (SAS) AF: 0.370 AC: 1784 AN: 4818

European-Finnish (FIN) AF: 0.302 AC: 3174 AN: 10524

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16652 AN: 67944

Other (OTH) AF: 0.277 AC: 585 AN: 2114

Alfa AF: 0.257 Hom.: 23226

Bravo AF: 0.246

Asia WGS AF: 0.414 AC: 1437 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Brugada syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.3
DANN	Benign	0.68
PhyloP100		0.77
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0
Splicevardb		2.0
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: rs17058639; hg19: chr3-57882601; COSMIC: COSV55844439; COSMIC: COSV55844439;