rs3750333

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001130438.3(SPTAN1):c.5437C>A(p.Arg1813Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0182 in 1,614,074 control chromosomes in the GnomAD database, including 447 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R1813R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.017 ( 34 hom., cov: 32)

Exomes 𝑓: 0.018 ( 413 hom. )

Consequence

SPTAN1
NM_001130438.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.99

Publications

7 publications found

Variant links:

Genes affected

SPTAN1 (HGNC:11273): (spectrin alpha, non-erythrocytic 1) Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]

SPTAN1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTAN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 9-128617719-C-A is Benign according to our data. Variant chr9-128617719-C-A is described in ClinVar as Benign. ClinVar VariationId is 160017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTAN1	NM_001130438.3 link	c.5437C>A	p.Arg1813Arg	synonymous_variant	Exon 42 of 57	ENST00000372739.7	NP_001123910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTAN1	ENST00000372739.7 link	c.5437C>A	p.Arg1813Arg	synonymous_variant	Exon 42 of 57	1	NM_001130438.3	ENSP00000361824.4

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2588

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.0659

Gnomad AMR

AF:

0.0417

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0803

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.0247

AC:

6195

AN:

251294

AF XY:

0.0233

show subpopulations

Gnomad AFR exome

AF:

0.00462

Gnomad AMR exome

AF:

0.0527

Gnomad ASJ exome

AF:

0.00715

Gnomad EAS exome

AF:

0.0833

Gnomad FIN exome

AF:

0.00481

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0183

AC:

26752

AN:

1461824

Hom.:

413

Cov.:

AF XY:

0.0183

AC XY:

13331

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00332

AC:

111

AN:

33474

American (AMR)

AF:

0.0507

AC:

2268

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00631

AC:

165

AN:

26136

East Asian (EAS)

AF:

0.0902

AC:

3580

AN:

39700

South Asian (SAS)

AF:

0.0234

AC:

2016

AN:

86254

European-Finnish (FIN)

AF:

0.00594

AC:

317

AN:

53410

Middle Eastern (MID)

AF:

0.0208

AC:

120

AN:

5760

European-Non Finnish (NFE)

AF:

0.0153

AC:

16971

AN:

1111980

Other (OTH)

AF:

0.0199

AC:

1204

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

1656

3312

4967

6623

8279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.0170

AC:

2592

AN:

152250

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1319

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00416

AC:

173

AN:

41556

American (AMR)

AF:

0.0419

AC:

641

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.0804

AC:

417

AN:

5184

South Asian (SAS)

AF:

0.0245

AC:

118

AN:

4816

European-Finnish (FIN)

AF:

0.00368

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0160

AC:

1087

AN:

68014

Other (OTH)

AF:

0.0166

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

124

247

371

494

618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0169

Hom.:

106

Bravo

AF:

0.0191

Asia WGS

AF:

0.0610

AC:

210

AN:

3478

EpiCase

AF:

0.0168

EpiControl

AF:

0.0169

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 04, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 05, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Developmental and epileptic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 5

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over