rs34706737

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_003126.4(SPTA1):c.2870C>T(p.Ala957Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,613,802 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 222 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 180 hom. )

Consequence

SPTA1
NM_003126.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.23

Publications

8 publications found

Variant links:

Genes affected

SPTA1 (HGNC:11272): (spectrin alpha, erythrocytic 1) This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

SPTA1 Gene-Disease associations (from GenCC):

hereditary spherocytosis type 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
elliptocytosis 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, PanelApp Australia, Labcorp Genetics (formerly Invitae)
pyropoikilocytosis, hereditary
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spherocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTA1 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 (MetaRNN=0.0038619936).

BP6

Variant 1-158656592-G-A is Benign according to our data. Variant chr1-158656592-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003126.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	NM_003126.4	MANE Select	c.2870C>T	p.Ala957Val	missense	Exon 20 of 52	NP_003117.2	P02549-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	ENST00000643759.2	MANE Select	c.2870C>T	p.Ala957Val	missense	Exon 20 of 52	ENSP00000495214.1	P02549-1
	SPTA1	ENST00000647256.1		n.*39C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4420

AN:

152144

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.00792

AC:

1976

AN:

249450

AF XY:

0.00621

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00495

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00330

AC:

4825

AN:

1461540

Hom.:

180

Cov.:

AF XY:

0.00295

AC XY:

2142

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.101

AC:

3382

AN:

33410

American (AMR)

AF:

0.00566

AC:

253

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0142

AC:

372

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000417

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00884

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000237

AC:

264

AN:

1111874

Other (OTH)

AF:

0.00773

AC:

467

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

240

481

721

962

1202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0290

AC:

4423

AN:

152262

Hom.:

222

Cov.:

AF XY:

0.0280

AC XY:

2083

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0990

AC:

4111

AN:

41538

American (AMR)

AF:

0.0112

AC:

171

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68036

Other (OTH)

AF:

0.0232

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

202

404

605

807

1009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0113

Hom.:

171

Bravo

AF:

0.0324

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0917

AC:

340

ESP6500EA

AF:

0.00134

AC:

ExAC

AF:

0.00940

AC:

1136

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Elliptocytosis 2 (1)

Hereditary spherocytosis type 3 (1)

not specified (1)

Pyropoikilocytosis, hereditary (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.46

Eigen

Benign

0.073

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

PhyloP100

3.2

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.15

Sift

Uncertain

0.022

Sift4G

Uncertain

0.0050

Polyphen

0.89

Vest4

0.52

MVP

0.75

MPC

0.21

ClinPred

0.065

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.18

Mutation Taster

=83/17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over