9-128617688-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001130438.3(SPTAN1):c.5406C>T(p.Thr1802=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,613,940 control chromosomes in the GnomAD database, including 593,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1802T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.73 ( 43790 hom., cov: 32)

Exomes 𝑓: 0.86 ( 549814 hom. )

Consequence

SPTAN1
NM_001130438.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.54

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 9-128617688-C-T is Benign according to our data. Variant chr9-128617688-C-T is described in ClinVar as [Benign]. Clinvar id is 139297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128617688-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTAN1	NM_001130438.3 linkuse as main transcript	c.5406C>T	p.Thr1802=	synonymous_variant	42/57	ENST00000372739.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTAN1	ENST00000372739.7 linkuse as main transcript	c.5406C>T	p.Thr1802=	synonymous_variant	42/57	1	NM_001130438.3	P3	Q13813-2

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110293

AN:

151990

Hom.:

43779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.771

GnomAD3 exomes

AF:

0.796

AC:

200115

AN:

251374

Hom.:

82649

AF XY:

0.807

AC XY:

109619

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.781

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.501

Gnomad SAS exome

AF:

0.767

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.900

Gnomad OTH exome

AF:

0.832

GnomAD4 exome

AF:

0.860

AC:

1257674

AN:

1461832

Hom.:

549814

Cov.:

AF XY:

0.860

AC XY:

625118

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.782

Gnomad4 ASJ exome

AF:

0.890

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.767

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.901

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.725

AC:

110319

AN:

152108

Hom.:

43790

Cov.:

AF XY:

0.722

AC XY:

53698

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.393

Gnomad4 AMR

AF:

0.783

Gnomad4 ASJ

AF:

0.894

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.742

Gnomad4 FIN

AF:

0.821

Gnomad4 NFE

AF:

0.901

Gnomad4 OTH

AF:

0.770

Alfa

AF:

0.866

Hom.:

82663

Bravo

AF:

0.707

Asia WGS

AF:

0.624

AC:

2170

AN:

3478

EpiCase

AF:

0.901

EpiControl

AF:

0.902

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 06, 2018

- -

Developmental and epileptic encephalopathy, 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

Cadd

Benign

0.010

Dann

Benign

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over