9-128584289-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PP3_ModerateBP6_Moderate

The NM_001130438.3(SPTAN1):c.2201T>C(p.Ile734Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPTAN1
NM_001130438.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.62

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.869

BP6

Variant 9-128584289-T-C is Benign according to our data. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128584289-T-C is described in CliVar as Likely_benign. Clinvar id is 461217.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTAN1	NM_001130438.3 link	c.2201T>C	p.Ile734Thr	missense_variant	Exon 17 of 57	ENST00000372739.7	NP_001123910.1	Q13813-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTAN1	ENST00000372739.7 link	c.2201T>C	p.Ile734Thr	missense_variant	Exon 17 of 57	1	NM_001130438.3	ENSP00000361824.4		Q13813-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy

Benign:1

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.87

D;D;D;D;D

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.9

M;.;M;M;.

PhyloP100

7.6

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.8

D;.;D;D;.

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0020

D;.;D;D;.

Sift4G

Uncertain

0.0090

D;T;D;T;D

Polyphen

1.0

D;.;P;D;.

Vest4

0.93

MutPred

0.63

Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);

MVP

0.87

MPC

1.9

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.53

gMVP

0.59

Mutation Taster

=47/53

disease causing

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over