Variant 5-132760922-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098811.2(SEPTIN8):c.1166G>A(p.Arg389Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,605,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

SEPTIN8
NM_001098811.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.534

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:

SEPTIN8 (HGNC:):

SEPTIN8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19801041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN8	NM_001098811.2 linkuse as main transcript	c.1166G>A	p.Arg389Gln	missense_variant	9/10	ENST00000378719.7	NP_001092281.1	Q92599-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN8	ENST00000378719.7 linkuse as main transcript	c.1166G>A	p.Arg389Gln	missense_variant	9/10	1	NM_001098811.2	ENSP00000367991.2		Q92599-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

238614

Hom.:

AF XY:

0.0000925

AC XY:

AN XY:

129700

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000243

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000434

AC:

AN:

1453172

Hom.:

Cov.:

AF XY:

0.0000470

AC XY:

AN XY:

722956

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.000117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.0000668

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000575

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000661

AC:

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

Jun 02, 2023

The c.1166G>A (p.R389Q) alteration is located in exon 9 (coding exon 9) of the SEPT8 gene. This alteration results from a G to A substitution at nucleotide position 1166, causing the arginine (R) at amino acid position 389 to be replaced by a glutamine (Q). 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

Benign

0.089

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

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

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.056

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.8

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

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.27

Sift

Benign

0.20

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

Sift4G

Benign

0.12

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

Polyphen

0.44

B;.;.;.;.;.;.;P;.

Vest4

0.37

MutPred

0.32

Loss of MoRF binding (P = 0.0457);.;Loss of MoRF binding (P = 0.0457);.;.;Loss of MoRF binding (P = 0.0457);.;.;Loss of MoRF binding (P = 0.0457);

MVP

0.76

MPC

0.68

ClinPred

0.051

GERP RS

3.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Varity_R

0.045

gMVP

0.20

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