rs786205846

Variant names:

• chr20-33443581-C-G
• 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. Variant got 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.

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000212

Gnomad4 OTH exome AF: 0.00

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
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-32031387;