Variant chr7-55805386-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_207366.3(SEPTIN14):c.991C>A(p.Gln331Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000924 in 1,572,128 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

SEPTIN14
NM_207366.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.40

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27479845).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN14	NM_207366.3 linkuse as main transcript	c.991C>A	p.Gln331Lys	missense_variant	9/10	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.991C>A	p.Gln331Lys	missense_variant	9/10	2	NM_207366.3	ENSP00000373627.3		Q6ZU15

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00157

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000497

AC:

101

AN:

203148

Hom.:

AF XY:

0.000504

AC XY:

AN XY:

109060

show subpopulations

Gnomad AFR exome

AF:

0.0000733

Gnomad AMR exome

AF:

0.000115

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000199

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.000194

GnomAD4 exome

AF:

0.000942

AC:

1337

AN:

1419974

Hom.:

Cov.:

AF XY:

0.000896

AC XY:

632

AN XY:

705244

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.000108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.000325

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000756

AC:

115

AN:

152154

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000932

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000367

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

Feb 05, 2024

The c.991C>A (p.Q331K) alteration is located in exon 9 (coding exon 8) of the SEPT14 gene. This alteration results from a C to A substitution at nucleotide position 991, causing the glutamine (Q) at amino acid position 331 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

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.022

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.097

MutationAssessor

Pathogenic

3.3

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.56

Sift

Benign

0.29

Sift4G

Benign

0.36

Polyphen

0.90

Vest4

0.62

MVP

0.86

MPC

0.48

ClinPred

0.24

GERP RS

2.9

Varity_R

0.38

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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