Variant 5-132761239-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.989G>A(p.Arg330Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SEPTIN8
NM_001098811.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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=0.24957609).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN8	NM_001098811.2 linkuse as main transcript	c.989G>A	p.Arg330Lys	missense_variant	8/10	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.989G>A	p.Arg330Lys	missense_variant	8/10	1	NM_001098811.2	ENSP00000367991.2		Q92599-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249248

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 25, 2024

The c.989G>A (p.R330K) alteration is located in exon 8 (coding exon 8) of the SEPT8 gene. This alteration results from a G to A substitution at nucleotide position 989, causing the arginine (R) at amino acid position 330 to be replaced by a lysine (K). 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

Uncertain

0.10

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

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

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

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

M_CAP

Benign

0.070

MetaRNN

Benign

0.25

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

MetaSVM

Uncertain

0.079

MutationAssessor

Uncertain

2.1

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

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

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

REVEL

Uncertain

0.48

Sift

Benign

0.063

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

Sift4G

Benign

0.10

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

Polyphen

0.51

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

Vest4

0.28

MutPred

0.39

Loss of loop (P = 0.0073);.;Loss of loop (P = 0.0073);.;.;Loss of loop (P = 0.0073);.;.;Loss of loop (P = 0.0073);

MVP

0.67

MPC

0.53

ClinPred

0.80

GERP RS

5.4

Varity_R

0.64

gMVP

0.54

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