rs786205847

Variant names:

• chr20-33443551-C-G
• rs786205847
• NM_003098.3:c.70G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-33443551-C-G
• chr20-33443551-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.70G>C​(p.Gly24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,185,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G24S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SNTA1 NM_003098.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• 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=0.19857448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTA1	NM_003098.3	c.70G>C	p.Gly24Arg	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.70G>C	p.Gly24Arg	missense_variant	Exon 1 of 8	1	NM_003098.3	ENSP00000217381.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1185882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 580684

African (AFR) AF: 0.00 AC: 0 AN: 24536

American (AMR) AF: 0.00 AC: 0 AN: 21976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19110

East Asian (EAS) AF: 0.00 AC: 0 AN: 23570

South Asian (SAS) AF: 0.00 AC: 0 AN: 52176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3274

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 968940

Other (OTH) AF: 0.00 AC: 0 AN: 46692

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.20
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.032	D
Polyphen		0.80	P
Vest4		0.16
MutPred		0.22		Gain of MoRF binding (P = 0.0416);
MVP		0.52
MPC		0.60
ClinPred		0.34	T
GERP RS		4.0
PromoterAI		0.016	Neutral
Varity_R		0.21
gMVP		0.52
Mutation Taster		=81/19	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: rs786205847; hg19: chr20-32031357;