20-33408164-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:2
• Conservation: PhyloP100: 1.20

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]

LOC124904889 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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 [Likely_benign]. Clinvar id is 338206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNTA1	NM_003098.3	c.*343G>A		3_prime_UTR_variant	8/8	ENST00000217381.3
LOC124904889	XR_007067567.1	n.95-1889C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNTA1	ENST00000217381.3	c.*343G>A		3_prime_UTR_variant	8/8	1	NM_003098.3	P1

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

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0498

Gnomad4 SAS exome AF: 0.00936

Gnomad4 FIN exome AF: 0.000715

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.0147

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

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0468

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0131 Hom.: 24

Bravo AF: 0.0342

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital long QT syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs41305789; hg19: chr20-31995970;