dbSNP rs140279996: SPTAN1:p.Pro1017Pro (chr9-128591521-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001130438.3(SPTAN1):c.3051G>A(p.Pro1017Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,614,100 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 5 hom. )

Consequence

SPTAN1
NM_001130438.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.99

Publications

4 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=-0.8).

BP6

Variant 9-128591521-G-A is Benign according to our data. Variant chr9-128591521-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00166 (253/152214) while in subpopulation EAS AF = 0.00869 (45/5176). AF 95% confidence interval is 0.00668. There are 0 homozygotes in GnomAd4. There are 124 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 253 AD gene.

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	HGVSp	Effect	Exon Rank	Protein
SPTAN1	NM_001130438.3	MANE Select	c.3051G>A	p.Pro1017Pro	synonymous	Exon 22 of 57	NP_001123910.1
SPTAN1	NM_001375318.1		c.3087G>A	p.Pro1029Pro	synonymous	Exon 23 of 59	NP_001362247.1
SPTAN1	NM_001375310.1		c.3051G>A	p.Pro1017Pro	synonymous	Exon 22 of 58	NP_001362239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPTAN1	ENST00000372739.7	TSL:1 MANE Select	c.3051G>A	p.Pro1017Pro	synonymous	Exon 22 of 57	ENSP00000361824.4
SPTAN1	ENST00000372731.8	TSL:1	c.3051G>A	p.Pro1017Pro	synonymous	Exon 22 of 56	ENSP00000361816.4
SPTAN1	ENST00000358161.9	TSL:1	c.3051G>A	p.Pro1017Pro	synonymous	Exon 22 of 55	ENSP00000350882.6

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

252

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00867

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00110

AC:

276

AN:

251494

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00962

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000395

AC:

577

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000359

AC XY:

261

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00433

AC:

145

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00665

AC:

264

AN:

39698

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000103

AC:

115

AN:

1112006

Other (OTH)

AF:

0.000315

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00166

AC:

253

AN:

152214

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00460

AC:

191

AN:

41518

American (AMR)

AF:

0.000458

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00869

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000922

Hom.:

Bravo

AF:

0.00203

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Developmental and epileptic encephalopathy, 5 (2)

Developmental and epileptic encephalopathy (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.24

(source)

DANN

Benign

0.64

PhyloP100

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=79/21

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