Variant 7-55796059-G-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 NM_207366.3(SEPTIN14):c.1153C>G(p.Gln385Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000295 in 1,356,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SEPTIN14
NM_207366.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69

Variant links:

Genes affected

SEPTIN14 (HGNC:33280): (septin 14) SEPT14 is a member of the highly conserved septin family of GTP-binding cytoskeletal proteins implicated in membrane transport, apoptosis, cell polarity, cell cycle regulation, cytokinesis, and other cellular functions (Peterson et al., 2007 [PubMed 17922164]).[supplied by OMIM, Jul 2008]

SEPTIN14 links:

Genome browser will be placed here

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=0.16264018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN14	NM_207366.3 linkuse as main transcript	c.1153C>G	p.Gln385Glu	missense_variant	10/10	ENST00000388975.4	NP_997249.2	Q6ZU15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN14	ENST00000388975.4 linkuse as main transcript	c.1153C>G	p.Gln385Glu	missense_variant	10/10	2	NM_207366.3	ENSP00000373627.3		Q6ZU15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000443

AC:

AN:

225686

Hom.:

AF XY:

0.00000803

AC XY:

AN XY:

124534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000571

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1356956

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 31, 2022

The c.1153C>G (p.Q385E) alteration is located in exon 10 (coding exon 9) of the SEPT14 gene. This alteration results from a C to G substitution at nucleotide position 1153, causing the glutamine (Q) at amino acid position 385 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

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.58

REVEL

Benign

0.26

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.40

Vest4

0.15

MutPred

0.13

Gain of relative solvent accessibility (P = 0.09);

MVP

0.64

MPC

0.25

ClinPred

0.35

GERP RS

1.3

Varity_R

0.091

gMVP

0.14

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