Variant chr2-109567910-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000397712.7(SEPTIN10):c.667A>G(p.Ile223Val) 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 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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
ENST00000397712.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

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=0.2140094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN10	NM_144710.5 linkuse as main transcript	c.667A>G	p.Ile223Val	missense_variant	6/11	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.667A>G	p.Ile223Val	missense_variant	6/11	1	NM_144710.5	ENSP00000380824		Q9P0V9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jan 12, 2024

The c.667A>G (p.I223V) alteration is located in exon 6 (coding exon 6) of the SEPT10 gene. This alteration results from a A to G substitution at nucleotide position 667, causing the isoleucine (I) at amino acid position 223 to be replaced by a valine (V). 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

0.080

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

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

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.68

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

M_CAP

Benign

0.0043

MetaRNN

Benign

0.21

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

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.9

.;L;.;.;.;.;.

MutationTaster

Benign

0.99

N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.42

N;N;N;N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.26

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

Sift4G

Benign

0.28

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

Polyphen

0.0050

B;B;B;.;.;.;.

Vest4

0.27

MutPred

0.29

Loss of methylation at K220 (P = 0.1174);Loss of methylation at K220 (P = 0.1174);.;.;Loss of methylation at K220 (P = 0.1174);.;.;

MVP

0.74

MPC

0.012

ClinPred

0.33

GERP RS

1.9

Varity_R

0.015

gMVP

0.24

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