rs34775878

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006946.4(SPTBN2):c.585C>T(p.Asn195Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,584 control chromosomes in the GnomAD database, including 9,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 729 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8736 hom. )

Consequence

SPTBN2
NM_006946.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.946

Publications

12 publications found

Variant links:

Genes affected

SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]

SPTBN2 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 14
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet
spinocerebellar ataxia type 5
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P

SPTBN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 11-66714162-G-A is Benign according to our data. Variant chr11-66714162-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 130372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.946 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN2	NM_006946.4 link	c.585C>T	p.Asn195Asn	synonymous_variant	Exon 7 of 38	ENST00000533211.6	NP_008877.2	O15020-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN2	ENST00000533211.6 link	c.585C>T	p.Asn195Asn	synonymous_variant	Exon 7 of 38	5	NM_006946.4	ENSP00000432568.1		O15020-1

Frequencies

GnomAD3 genomes

AF:

0.0799

AC:

12163

AN:

152196

Hom.:

728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.0969

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0458

Gnomad FIN

AF:

0.0304

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0814

AC:

20466

AN:

251456

AF XY:

0.0840

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.0694

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0333

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.103

AC:

149905

AN:

1461270

Hom.:

8736

Cov.:

AF XY:

0.102

AC XY:

74007

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.0202

AC:

677

AN:

33476

American (AMR)

AF:

0.0725

AC:

3242

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3283

AN:

26128

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.0452

AC:

3902

AN:

86254

European-Finnish (FIN)

AF:

0.0354

AC:

1889

AN:

53410

Middle Eastern (MID)

AF:

0.142

AC:

818

AN:

5768

European-Non Finnish (NFE)

AF:

0.117

AC:

129828

AN:

1111424

Other (OTH)

AF:

0.104

AC:

6254

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

7249

14498

21746

28995

36244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0798

AC:

12158

AN:

152314

Hom.:

729

Cov.:

AF XY:

0.0766

AC XY:

5705

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0218

AC:

905

AN:

41580

American (AMR)

AF:

0.0968

AC:

1481

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0456

AC:

220

AN:

4824

European-Finnish (FIN)

AF:

0.0304

AC:

323

AN:

10614

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8211

AN:

68016

Other (OTH)

AF:

0.101

AC:

214

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

565

1130

1695

2260

2825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.107

Hom.:

501

Bravo

AF:

0.0838

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.134

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Spinocerebellar ataxia type 5

Benign:1

Apr 14, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant cerebellar ataxia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

-0.37

CADD

Benign

9.0

(source)

DANN

Benign

0.86

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs34775878

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