20-33408164-C-T

Variant names:

• chr20-33408164-C-T
• rs41305789
• NM_003098.3:c.*343G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003098.3(SNTA1):​c.*343G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 367,110 control chromosomes in the GnomAD database, including 557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (237 hom., cov: 32)
  • Exomes 𝑓: 0.017 (320 hom.)
• Consequence: SNTA1 NM_003098.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.20
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 20-33408164-C-T is Benign according to our data. Variant chr20-33408164-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 338206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

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.*343G>A		3_prime_UTR	Exon 8 of 8	NP_003089.1	Q13424-1
	SNTA1	NM_001424413.1		c.*343G>A		3_prime_UTR	Exon 8 of 8	NP_001411342.1
	SNTA1	NM_001424414.1		c.*402G>A		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.*343G>A		3_prime_UTR	Exon 8 of 8	ENSP00000217381.2	Q13424-1
	SNTA1	ENST00000953204.1		c.*343G>A		3_prime_UTR	Exon 9 of 9	ENSP00000623263.1
	SNTA1	ENST00000953205.1		c.*343G>A		3_prime_UTR	Exon 9 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3270 AN: 152134 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0171 AC: 3681 AN: 214858 Hom.: 320 Cov.: 0 AF XY: 0.0152 AC XY: 1740 AN XY: 114148

African (AFR) AF: 0.0157 AC: 104 AN: 6630

American (AMR) AF: 0.210 AC: 2318 AN: 11032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6056

East Asian (EAS) AF: 0.0498 AC: 588 AN: 11810

South Asian (SAS) AF: 0.00936 AC: 324 AN: 34622

European-Finnish (FIN) AF: 0.000715 AC: 7 AN: 9792

Middle Eastern (MID) AF: 0.00355 AC: 3 AN: 846

European-Non Finnish (NFE) AF: 0.00137 AC: 168 AN: 122584

Other (OTH) AF: 0.0147 AC: 169 AN: 11486

GnomAD4 genome AF: 0.0216 AC: 3284 AN: 152252 Hom.: 237 Cov.: 32 AF XY: 0.0231 AC XY: 1718 AN XY: 74424

African (AFR) AF: 0.0153 AC: 634 AN: 41556

American (AMR) AF: 0.145 AC: 2209 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0468 AC: 242 AN: 5176

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4824

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00135 AC: 92 AN: 68008

Other (OTH) AF: 0.0213 AC: 45 AN: 2116

Alfa AF: 0.0133 Hom.: 24

Bravo AF: 0.0342

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome 12 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		1.2
Mutation Taster		=99/1	polymorphism (auto)

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: rs41305789; hg19: chr20-31995970;