9-128626364-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130438.3(SPTAN1):c.6280-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,611,742 control chromosomes in the GnomAD database, including 590,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 43339 hom., cov: 32)

Exomes 𝑓: 0.86 ( 546773 hom. )

Consequence

SPTAN1
NM_001130438.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.617

Publications

11 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neuronopathy, distal hereditary motor, autosomal dominant 11
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spastic paraplegia
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

SPTAN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-128626364-C-T is Benign according to our data. Variant chr9-128626364-C-T is described in ClinVar as Benign. ClinVar VariationId is 160021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPTAN1	NM_001130438.3	MANE Select	c.6280-27C>T	intron	N/A	NP_001123910.1	Q13813-2
SPTAN1	NM_001375318.1		c.6316-27C>T	intron	N/A	NP_001362247.1
SPTAN1	NM_001375310.1		c.6280-27C>T	intron	N/A	NP_001362239.1	A0A994J6W3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPTAN1	ENST00000372739.7	TSL:1 MANE Select	c.6280-27C>T	intron	N/A	ENSP00000361824.4	Q13813-2
SPTAN1	ENST00000372731.8	TSL:1	c.6265-27C>T	intron	N/A	ENSP00000361816.4	Q13813-1
SPTAN1	ENST00000358161.9	TSL:1	c.6205-27C>T	intron	N/A	ENSP00000350882.6	Q13813-3

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109285

AN:

152030

Hom.:

43327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.781

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.753

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.767

GnomAD2 exomes

AF:

0.795

AC:

196830

AN:

247550

AF XY:

0.807

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

0.520

Gnomad FIN exome

AF:

0.817

Gnomad NFE exome

AF:

0.897

Gnomad OTH exome

AF:

0.831

GnomAD4 exome

AF:

0.859

AC:

1253250

AN:

1459594

Hom.:

546773

Cov.:

AF XY:

0.858

AC XY:

623315

AN XY:

726168

show subpopulations

African (AFR)

AF:

0.349

AC:

11668

AN:

33446

American (AMR)

AF:

0.784

AC:

35043

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.890

AC:

23260

AN:

26136

East Asian (EAS)

AF:

0.502

AC:

19942

AN:

39696

South Asian (SAS)

AF:

0.778

AC:

67033

AN:

86186

European-Finnish (FIN)

AF:

0.828

AC:

43154

AN:

52110

Middle Eastern (MID)

AF:

0.817

AC:

4205

AN:

5150

European-Non Finnish (NFE)

AF:

0.899

AC:

999232

AN:

1111854

Other (OTH)

AF:

0.824

AC:

49713

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10118

20237

30355

40474

50592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21238

42476

63714

84952

106190

<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:

0.718

AC:

109317

AN:

152148

Hom.:

43339

Cov.:

AF XY:

0.716

AC XY:

53229

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.370

AC:

15362

AN:

41502

American (AMR)

AF:

0.782

AC:

11961

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

3103

AN:

3472

East Asian (EAS)

AF:

0.530

AC:

2725

AN:

5146

South Asian (SAS)

AF:

0.753

AC:

3636

AN:

4830

European-Finnish (FIN)

AF:

0.817

AC:

8654

AN:

10586

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61142

AN:

67996

Other (OTH)

AF:

0.766

AC:

1620

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1146

2292

3438

4584

5730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.822

Hom.:

18488

Bravo

AF:

0.700

Asia WGS

AF:

0.625

AC:

2174

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.25

(source)

DANN

Benign

0.59

PhyloP100

-0.62

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over