Variant chr2-109553178-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_144710.5(SEPTIN10):c.1070G>A(p.Gly357Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SEPTIN10
NM_144710.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

Variant links:

Genes affected

SEPTIN10 (HGNC:14349): (septin 10) This gene encodes a member of the septin family of cytoskeletal proteins with GTPase activity. This protein localizes to the cytoplasm and nucleus and displays GTP-binding and GTPase activity. A pseudogene for this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

SEPTIN10 links:

RANBP2 (HGNC:):

RANBP2 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=0.09829697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN10	NM_144710.5 linkuse as main transcript	c.1070G>A	p.Gly357Asp	missense_variant	9/11	ENST00000397712.7	NP_653311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN10	ENST00000397712.7 linkuse as main transcript	c.1070G>A	p.Gly357Asp	missense_variant	9/11	1	NM_144710.5	ENSP00000380824		Q9P0V9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

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

Nov 29, 2021

The c.1070G>A (p.G357D) alteration is located in exon 9 (coding exon 9) of the SEPT10 gene. This alteration results from a G to A substitution at nucleotide position 1070, causing the glycine (G) at amino acid position 357 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.0089

T;T;.;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.098

T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.4

.;L;.;.;.

MutationTaster

Benign

0.64

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

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Benign

0.48

T;T;T;T;T

Polyphen

0.0030

B;B;B;.;.

Vest4

0.31

MutPred

0.26

Loss of MoRF binding (P = 0.0583);Loss of MoRF binding (P = 0.0583);.;.;Loss of MoRF binding (P = 0.0583);

MVP

0.70

MPC

0.012

ClinPred

0.069

GERP RS

4.3

Varity_R

0.062

gMVP

0.34

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