rs886038523

Variant names:

• chr20-33443392-G-A
• rs886038523
• NM_003098.3:c.229C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_003098.3(SNTA1):​c.229C>T​(p.Leu77Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNTA1 NM_003098.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.43
• Publications: 0 publications found

Genes affected

SNTA1 (HGNC:11167): (syntrophin alpha 1) Syntrophins are cytoplasmic peripheral membrane scaffold proteins that are components of the dystrophin-associated protein complex. This gene is a member of the syntrophin gene family and encodes the most common syntrophin isoform found in cardiac tissues. The N-terminal PDZ domain of this syntrophin protein interacts with the C-terminus of the pore-forming alpha subunit (SCN5A) of the cardiac sodium channel Nav1.5. This protein also associates cardiac sodium channels with the nitric oxide synthase-PMCA4b (plasma membrane Ca-ATPase subtype 4b) complex in cardiomyocytes. This gene is a susceptibility locus for Long-QT syndrome (LQT) - an inherited disorder associated with sudden cardiac death from arrhythmia - and sudden infant death syndrome (SIDS). This protein also associates with dystrophin and dystrophin-related proteins at the neuromuscular junction and alters intracellular calcium ion levels in muscle tissue. [provided by RefSeq, Jan 2013]

SNTA1 Gene-Disease associations (from GenCC):

• long QT syndrome 12

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 20-33443392-G-A is Benign according to our data. Variant chr20-33443392-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 258904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.43 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003098.3. 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
	SNTA1	NM_003098.3	MANE Select	c.229C>T	p.Leu77Leu	synonymous	Exon 1 of 8	NP_003089.1	Q13424-1
	SNTA1	NM_001424413.1		c.229C>T	p.Leu77Leu	synonymous	Exon 1 of 8	NP_001411342.1
	SNTA1	NM_001424414.1		c.229C>T	p.Leu77Leu	synonymous	Exon 1 of 8	NP_001411343.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTA1	ENST00000217381.3	TSL:1 MANE Select	c.229C>T	p.Leu77Leu	synonymous	Exon 1 of 8	ENSP00000217381.2	Q13424-1
	SNTA1	ENST00000953204.1		c.229C>T	p.Leu77Leu	synonymous	Exon 1 of 9	ENSP00000623263.1
	SNTA1	ENST00000953205.1		c.229C>T	p.Leu77Leu	synonymous	Exon 1 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1221344 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 598620

African (AFR) AF: 0.00 AC: 0 AN: 24110

American (AMR) AF: 0.00 AC: 0 AN: 12234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18438

East Asian (EAS) AF: 0.00 AC: 0 AN: 26778

South Asian (SAS) AF: 0.00 AC: 0 AN: 55372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3396

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1001862

Other (OTH) AF: 0.00 AC: 0 AN: 49752

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		2.4
PromoterAI		-0.019	Neutral
Mutation Taster		=96/4	polymorphism

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: rs886038523; hg19: chr20-32031198;