Variant 5-132760877-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001098811.2(SEPTIN8):c.1211C>A(p.Ala404Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,612,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

SEPTIN8
NM_001098811.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.40

Variant links:

Genes affected

SEPTIN8 (HGNC:16511): (septin 8) This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

SEPTIN8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN8	NM_001098811.2 linkuse as main transcript	c.1211C>A	p.Ala404Glu	missense_variant	9/10	ENST00000378719.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN8	ENST00000378719.7 linkuse as main transcript	c.1211C>A	p.Ala404Glu	missense_variant	9/10	1	NM_001098811.2	P3	Q92599-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000178

AC:

AN:

247222

Hom.:

AF XY:

0.000186

AC XY:

AN XY:

134286

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000347

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000333

AC:

487

AN:

1460278

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

726532

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000939

Gnomad4 NFE exome

AF:

0.000422

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000118

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.1211C>A (p.A404E) alteration is located in exon 9 (coding exon 9) of the SEPT8 gene. This alteration results from a C to A substitution at nucleotide position 1211, causing the alanine (A) at amino acid position 404 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.072

T;.;.;T;.;.;.;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;D;D;D;.;D;D;D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.60

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.049

MutationAssessor

Uncertain

2.3

M;.;M;.;.;.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;N;N;.;N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.10

T;T;T;.;T;T;T;T;T

Sift4G

Benign

0.16

T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;.;.;.;.;.;.;D;.

Vest4

0.90

MVP

0.93

MPC

1.1

ClinPred

0.30

GERP RS

5.3

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.26

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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