chr20-33408493-G-A

Variant names:

• chr20-33408493-G-A
• rs761196972
• NM_003098.3:c.*14C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003098.3(SNTA1):​c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,589,594 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (0 hom.)
• Consequence: SNTA1 NM_003098.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800
• 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

ENSG00000288878 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-33408493-G-A is Benign according to our data. Variant chr20-33408493-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 381756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 91 AD gene.

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.*14C>T		3_prime_UTR	Exon 8 of 8	NP_003089.1	Q13424-1
	SNTA1	NM_001424413.1		c.*14C>T		3_prime_UTR	Exon 8 of 8	NP_001411342.1
	SNTA1	NM_001424414.1		c.*73C>T		3_prime_UTR	Exon 8 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.*14C>T		3_prime_UTR	Exon 8 of 8	ENSP00000217381.2	Q13424-1
	SNTA1	ENST00000953204.1		c.*14C>T		3_prime_UTR	Exon 9 of 9	ENSP00000623263.1
	SNTA1	ENST00000953205.1		c.*14C>T		3_prime_UTR	Exon 9 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250938 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000633 AC: 91 AN: 1437400 Hom.: 0 Cov.: 27 AF XY: 0.0000642 AC XY: 46 AN XY: 716702

African (AFR) AF: 0.0000303 AC: 1 AN: 32986

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000762 AC: 83 AN: 1089710

Other (OTH) AF: 0.000117 AC: 7 AN: 59620

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-0.080

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: rs761196972; hg19: chr20-31996299;