9-128617688-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001130438.3(SPTAN1):c.5406C>T(p.Thr1802Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,613,940 control chromosomes in the GnomAD database, including 593,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1802T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.73 ( 43790 hom., cov: 32)

Exomes 𝑓: 0.86 ( 549814 hom. )

Consequence

SPTAN1
NM_001130438.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.54

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 9-128617688-C-T is Benign according to our data. Variant chr9-128617688-C-T is described in ClinVar as Benign. ClinVar VariationId is 139297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTAN1	NM_001130438.3 link	c.5406C>T	p.Thr1802Thr	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.5406C>T	p.Thr1802Thr	synonymous_variant	Exon 42 of 57	1	NM_001130438.3	ENSP00000361824.4

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110293

AN:

151990

Hom.:

43779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.771

GnomAD2 exomes

AF:

0.796

AC:

200115

AN:

251374

AF XY:

0.807

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.781

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.900

Gnomad OTH exome

AF:

0.832

GnomAD4 exome

AF:

0.860

AC:

1257674

AN:

1461832

Hom.:

549814

Cov.:

AF XY:

0.860

AC XY:

625118

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.371

AC:

12409

AN:

33472

American (AMR)

AF:

0.782

AC:

34988

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.890

AC:

23261

AN:

26136

East Asian (EAS)

AF:

0.490

AC:

19431

AN:

39694

South Asian (SAS)

AF:

0.767

AC:

66188

AN:

86252

European-Finnish (FIN)

AF:

0.832

AC:

44419

AN:

53410

Middle Eastern (MID)

AF:

0.810

AC:

4669

AN:

5766

European-Non Finnish (NFE)

AF:

0.901

AC:

1002428

AN:

1111994

Other (OTH)

AF:

0.826

AC:

49881

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

10415

20831

31246

41662

52077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21256

42512

63768

85024

106280

<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:

0.725

AC:

110319

AN:

152108

Hom.:

43790

Cov.:

AF XY:

0.722

AC XY:

53698

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.393

AC:

16283

AN:

41440

American (AMR)

AF:

0.783

AC:

11971

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

3101

AN:

3470

East Asian (EAS)

AF:

0.514

AC:

2656

AN:

5172

South Asian (SAS)

AF:

0.742

AC:

3574

AN:

4818

European-Finnish (FIN)

AF:

0.821

AC:

8702

AN:

10596

Middle Eastern (MID)

AF:

0.810

AC:

238

AN:

294

European-Non Finnish (NFE)

AF:

0.901

AC:

61299

AN:

68010

Other (OTH)

AF:

0.770

AC:

1622

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1164

2328

3492

4656

5820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.850

Hom.:

112856

Bravo

AF:

0.707

Asia WGS

AF:

0.624

AC:

2170

AN:

3478

EpiCase

AF:

0.901

EpiControl

AF:

0.902

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported. -

Jun 12, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

May 06, 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

- -

Inborn genetic diseases

Benign:1

Dec 31, 2015

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

Benign

-0.69

CADD

Benign

0.010

(source)

DANN

Benign

0.29

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

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

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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