rs786205846

Variant names:

• chr20-33443581-C-G
• rs786205846
• NM_003098.3:c.40G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-33443581-C-G
• chr20-33443581-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003098.3(SNTA1):​c.40G>C​(p.Glu14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000177 in 1,131,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E14K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SNTA1 NM_003098.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2424486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTA1	NM_003098.3	c.40G>C	p.Glu14Gln	missense_variant	Exon 1 of 8	ENST00000217381.3	NP_003089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTA1	ENST00000217381.3	c.40G>C	p.Glu14Gln	missense_variant	Exon 1 of 8	1	NM_003098.3	ENSP00000217381.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1131130 Hom.: 0 Cov.: 31 AF XY: 0.00000181 AC XY: 1 AN XY: 551194

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22394

American (AMR) AF: 0.00 AC: 0 AN: 13536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16062

East Asian (EAS) AF: 0.00 AC: 0 AN: 22236

South Asian (SAS) AF: 0.00 AC: 0 AN: 41682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3028

European-Non Finnish (NFE) AF: 0.00000212 AC: 2 AN: 944776

Other (OTH) AF: 0.00 AC: 0 AN: 43958

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.86	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.098
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		0.84	P
Vest4		0.18
MutPred		0.25		Gain of MoRF binding (P = 0.0603);
MVP		0.53
MPC		0.93
ClinPred		0.86	D
GERP RS		2.6
PromoterAI		0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.67
Mutation Taster		=86/14	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: rs786205846; hg19: chr20-32031387;