chr9-128598471-C-T

Position:

chr9-128598471-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.3486C>T(p.Leu1162Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,611,482 control chromosomes in the GnomAD database, including 595,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 45441 hom., cov: 31)

Exomes 𝑓: 0.86 ( 550039 hom. )

Consequence

SPTAN1
NM_001130438.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0580

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:

SPTAN1 (HGNC:):

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 9-128598471-C-T is Benign according to our data. Variant chr9-128598471-C-T is described in ClinVar as [Benign]. Clinvar id is 160009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128598471-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.058 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	Protein	UniProt
SPTAN1	NM_001130438.3 linkuse as main transcript	c.3486C>T	p.Leu1162Leu	synonymous_variant	25/57	ENST00000372739.7	NP_001123910.1	Q13813-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTAN1	ENST00000372739.7 linkuse as main transcript	c.3486C>T	p.Leu1162Leu	synonymous_variant	25/57	1	NM_001130438.3	ENSP00000361824.4		Q13813-2

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

113964

AN:

151886

Hom.:

45431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.753

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.790

GnomAD3 exomes

AF:

0.804

AC:

199258

AN:

247968

Hom.:

82425

AF XY:

0.813

AC XY:

108827

AN XY:

133898

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.787

Gnomad ASJ exome

AF:

0.894

Gnomad EAS exome

AF:

0.505

Gnomad SAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.819

Gnomad NFE exome

AF:

0.898

Gnomad OTH exome

AF:

0.835

GnomAD4 exome

AF:

0.863

AC:

1258911

AN:

1459478

Hom.:

550039

Cov.:

AF XY:

0.862

AC XY:

625553

AN XY:

725832

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.790

Gnomad4 ASJ exome

AF:

0.892

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.778

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.900

Gnomad4 OTH exome

AF:

0.832

GnomAD4 genome

AF:

0.750

AC:

113998

AN:

152004

Hom.:

45441

Cov.:

AF XY:

0.746

AC XY:

55432

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.792

Gnomad4 ASJ

AF:

0.895

Gnomad4 EAS

AF:

0.519

Gnomad4 SAS

AF:

0.753

Gnomad4 FIN

AF:

0.821

Gnomad4 NFE

AF:

0.901

Gnomad4 OTH

AF:

0.789

Alfa

AF:

0.846

Hom.:

28168

Bravo

AF:

0.735

Asia WGS

AF:

0.637

AC:

2215

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 91. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 06, 2018	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

5.3

DANN

Benign

0.58

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