rs572545726

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003098.3(SNTA1):c.221C>T(p.Pro74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,359,300 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P74S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

SNTA1
NM_003098.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:11

Conservation

PhyloP100: 2.61

Publications

8 publications found

Variant links:

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

SNTA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006747484).

BP6

Variant 20-33443400-G-A is Benign according to our data. Variant chr20-33443400-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 263476.

BS2

High AC in GnomAd4 at 296 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNTA1	NM_003098.3	MANE Select	c.221C>T	p.Pro74Leu	missense	Exon 1 of 8	NP_003089.1	Q13424-1
SNTA1	NM_001424413.1		c.221C>T	p.Pro74Leu	missense	Exon 1 of 8	NP_001411342.1
SNTA1	NM_001424414.1		c.221C>T	p.Pro74Leu	missense	Exon 1 of 8	NP_001411343.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNTA1	ENST00000217381.3	TSL:1 MANE Select	c.221C>T	p.Pro74Leu	missense	Exon 1 of 8	ENSP00000217381.2	Q13424-1
SNTA1	ENST00000953204.1		c.221C>T	p.Pro74Leu	missense	Exon 1 of 9	ENSP00000623263.1
SNTA1	ENST00000953205.1		c.221C>T	p.Pro74Leu	missense	Exon 1 of 9	ENSP00000623264.1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

296

AN:

151818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000857

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00217

AC:

AN:

19810

AF XY:

0.00226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000631

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000632

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.00194

GnomAD4 exome

AF:

0.00231

AC:

2786

AN:

1207374

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

1344

AN XY:

590826

show subpopulations

African (AFR)

AF:

0.000422

AC:

AN:

23706

American (AMR)

AF:

0.000746

AC:

AN:

10724

Ashkenazi Jewish (ASJ)

AF:

0.000174

AC:

AN:

17270

East Asian (EAS)

AF:

0.00

AC:

AN:

26578

South Asian (SAS)

AF:

0.000551

AC:

AN:

52656

European-Finnish (FIN)

AF:

0.000907

AC:

AN:

28672

Middle Eastern (MID)

AF:

0.00241

AC:

AN:

3314

European-Non Finnish (NFE)

AF:

0.00261

AC:

2599

AN:

995370

Other (OTH)

AF:

0.00210

AC:

103

AN:

49084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

138

276

414

552

690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00195

AC:

296

AN:

151926

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.000482

AC:

AN:

41514

American (AMR)

AF:

0.00125

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000857

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00337

AC:

229

AN:

67900

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00179

ExAC

AF:

0.00103

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Long QT syndrome 12 (3)

not specified (3)

not provided (2)

Cardiovascular phenotype (1)

Long QT syndrome (1)

SNTA1-related disorder (1)

Ventricular tachycardia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

2.6

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.5

REVEL

Benign

0.055

Sift

Benign

0.032

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.071

MVP

0.52

MPC

0.29

ClinPred

0.026

GERP RS

2.5

PromoterAI

-0.094

Neutral

(source)

Varity_R

0.053

gMVP

0.29

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over