chr20-33408165-G-A

Variant names:

• chr20-33408165-G-A
• rs150740903
• NM_003098.3:c.*342C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003098.3(SNTA1):​c.*342C>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 0.00415 in 366,034 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: SNTA1 NM_003098.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.72
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-33408165-G-A is Benign according to our data. Variant chr20-33408165-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 338207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00835 (1272/152308) while in subpopulation AFR AF = 0.0278 (1156/41554). AF 95% confidence interval is 0.0265. There are 16 homozygotes in GnomAd4. There are 612 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1272 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.*342C>T		3_prime_UTR	Exon 8 of 8	NP_003089.1	Q13424-1
	SNTA1	NM_001424413.1		c.*342C>T		3_prime_UTR	Exon 8 of 8	NP_001411342.1
	SNTA1	NM_001424414.1		c.*401C>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.*342C>T		3_prime_UTR	Exon 8 of 8	ENSP00000217381.2	Q13424-1
	SNTA1	ENST00000953204.1		c.*342C>T		3_prime_UTR	Exon 9 of 9	ENSP00000623263.1
	SNTA1	ENST00000953205.1		c.*342C>T		3_prime_UTR	Exon 9 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes AF: 0.00837 AC: 1274 AN: 152190 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00116 AC: 247 AN: 213726 Hom.: 3 Cov.: 0 AF XY: 0.000971 AC XY: 110 AN XY: 113246

African (AFR) AF: 0.0256 AC: 171 AN: 6686

American (AMR) AF: 0.00413 AC: 46 AN: 11148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6118

East Asian (EAS) AF: 0.00 AC: 0 AN: 12040

South Asian (SAS) AF: 0.0000297 AC: 1 AN: 33662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9768

Middle Eastern (MID) AF: 0.00119 AC: 1 AN: 838

European-Non Finnish (NFE) AF: 0.0000492 AC: 6 AN: 121972

Other (OTH) AF: 0.00191 AC: 22 AN: 11494

GnomAD4 genome AF: 0.00835 AC: 1272 AN: 152308 Hom.: 16 Cov.: 32 AF XY: 0.00822 AC XY: 612 AN XY: 74470

African (AFR) AF: 0.0278 AC: 1156 AN: 41554

American (AMR) AF: 0.00569 AC: 87 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00569 Hom.: 3

Bravo AF: 0.00945

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.68
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs150740903; hg19: chr20-31995971; COSMIC: COSV99458988;