rs140279996

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001130438.3(SPTAN1):c.3051G>A(p.Pro1017=) 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:9

Conservation

PhyloP100: -3.99

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 -17 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 [Likely_benign]. Clinvar id is 139282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128591521-G-A is described in Lovd as [Likely_benign].

BP7

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

BS2

High AC in GnomAd4 at 253 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTAN1	NM_001130438.3 linkuse as main transcript	c.3051G>A	p.Pro1017=	synonymous_variant	22/57	ENST00000372739.7	NP_001123910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTAN1	ENST00000372739.7 linkuse as main transcript	c.3051G>A	p.Pro1017=	synonymous_variant	22/57	1	NM_001130438.3	ENSP00000361824	P3	Q13813-2

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

GnomAD3 exomes

AF:

0.00110

AC:

276

AN:

251494

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135922

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 SAS exome

AF:

0.0000653

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

Gnomad4 AFR exome

AF:

0.00433

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00665

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00166

AC:

253

AN:

152214

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00460

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00869

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000903

Hom.:

Bravo

AF:

0.00203

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 13, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 21, 2018	- -

Developmental and epileptic encephalopathy, 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	Aug 18, 2022	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.4% (190/41396) (https://gnomad.broadinstitute.org/variant/9-128591521-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Benign (Variation ID:139282). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2016

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

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.24

DANN

Benign

0.64

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