rs138863915

Variant names:

• chr20-33412352-G-A
• rs138863915
• NM_003098.3:c.984C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-33412352-G-A
• chr20-33412352-G-C
• chr20-33412352-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_003098.3(SNTA1):​c.984C>T​(p.Pro328Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,611,628 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P328P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: SNTA1 NM_003098.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.932
• 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

LOC124904889 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 20-33412352-G-A is Benign according to our data. Variant chr20-33412352-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 139222.
• BP7: Synonymous conserved (PhyloP=-0.932 with no splicing effect.
• BS2: High AC in GnomAd4 at 172 AD gene.

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.984C>T	p.Pro328Pro	synonymous	Exon 5 of 8	NP_003089.1	Q13424-1
	SNTA1	NM_001424413.1		c.984C>T	p.Pro328Pro	synonymous	Exon 5 of 8	NP_001411342.1
	SNTA1	NM_001424414.1		c.984C>T	p.Pro328Pro	synonymous	Exon 5 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.984C>T	p.Pro328Pro	synonymous	Exon 5 of 8	ENSP00000217381.2	Q13424-1
	SNTA1	ENST00000953204.1		c.1107C>T	p.Pro369Pro	synonymous	Exon 6 of 9	ENSP00000623263.1
	SNTA1	ENST00000953205.1		c.1053C>T	p.Pro351Pro	synonymous	Exon 6 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000923 AC: 224 AN: 242722 AF XY: 0.000948

Gnomad AFR exome AF: 0.0000653

Gnomad AMR exome AF: 0.000325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00235

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00101 AC: 1469 AN: 1459342 Hom.: 2 Cov.: 33 AF XY: 0.00101 AC XY: 735 AN XY: 725726

African (AFR) AF: 0.000149 AC: 5 AN: 33462

American (AMR) AF: 0.000316 AC: 14 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85692

European-Finnish (FIN) AF: 0.00281 AC: 149 AN: 53068

Middle Eastern (MID) AF: 0.000536 AC: 3 AN: 5598

European-Non Finnish (NFE) AF: 0.00111 AC: 1239 AN: 1111304

Other (OTH) AF: 0.000930 AC: 56 AN: 60234

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00115 AC XY: 86 AN XY: 74462

African (AFR) AF: 0.000168 AC: 7 AN: 41566

American (AMR) AF: 0.000458 AC: 7 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.000733

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Cardiovascular phenotype (1)
-	1	-	Congenital long QT syndrome (1)
-	-	1	Long QT syndrome (1)
-	-	1	Long QT syndrome 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.1
DANN	Benign	0.53
PhyloP100		-0.93
Mutation Taster		=100/0	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: rs138863915; hg19: chr20-32000158;