Genetic Variant SPTAN1:p.Gly1958Ser (chr9-128624367-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130438.3(SPTAN1):c.5872G>A(p.Gly1958Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1958D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SPTAN1
NM_001130438.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.56

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTAN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15499637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPTAN1	NM_001130438.3	MANE Select	c.5872G>A	p.Gly1958Ser	missense	Exon 46 of 57	NP_001123910.1
SPTAN1	NM_001375318.1		c.5908G>A	p.Gly1970Ser	missense	Exon 47 of 59	NP_001362247.1
SPTAN1	NM_001375310.1		c.5872G>A	p.Gly1958Ser	missense	Exon 46 of 58	NP_001362239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPTAN1	ENST00000372739.7	TSL:1 MANE Select	c.5872G>A	p.Gly1958Ser	missense	Exon 46 of 57	ENSP00000361824.4
SPTAN1	ENST00000372731.8	TSL:1	c.5857G>A	p.Gly1953Ser	missense	Exon 45 of 56	ENSP00000361816.4
SPTAN1	ENST00000358161.9	TSL:1	c.5797G>A	p.Gly1933Ser	missense	Exon 44 of 55	ENSP00000350882.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251246

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.076

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.86

M_CAP

Benign

0.0042

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.36

PhyloP100

5.6

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.12

REVEL

Benign

0.059

Sift

Benign

0.74

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.32

MutPred

0.28

Gain of phosphorylation at G1953 (P = 0.0526)

MVP

0.32

MPC

0.78

ClinPred

0.37

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

gMVP

0.18

Mutation Taster

=87/13

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over