7-35903145-C-T

Position:

chr7-35903145-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001788.6(SEPTIN7):c.1204C>T(p.Arg402Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,600,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SEPTIN7
NM_001788.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

SEPTIN7 (HGNC:1717): (septin 7) This gene encodes a protein that is highly similar to the CDC10 protein of Saccharomyces cerevisiae. The protein also shares similarity with Diff 6 of Drosophila and with H5 of mouse. Each of these similar proteins, including the yeast CDC10, contains a GTP-binding motif. The yeast CDC10 protein is a structural component of the 10 nm filament which lies inside the cytoplasmic membrane and is essential for cytokinesis. This human protein functions in gliomagenesis and in the suppression of glioma cell growth, and it is required for the association of centromere-associated protein E with the kinetochore. Alternative splicing results in multiple transcript variants. Several related pseudogenes have been identified on chromosomes 5, 7, 9, 10, 11, 14, 17 and 19. [provided by RefSeq, Jul 2011]

SEPTIN7 links:

SEPTIN7 (HGNC:):

SEPTIN7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 linkuse as main transcript	c.1204C>T	p.Arg402Cys	missense_variant	13/14	ENST00000350320.11	NP_001779.3	Q16181-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEPTIN7	ENST00000350320.11 linkuse as main transcript	c.1204C>T	p.Arg402Cys	missense_variant	13/14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635175.1 linkuse as main transcript	n.*1121C>T		non_coding_transcript_exon_variant	13/14	2		ENSP00000489192.1	A0A0U1RQW0
SEPTIN7	ENST00000635175.1 linkuse as main transcript	n.*1121C>T		3_prime_UTR_variant	13/14	2		ENSP00000489192.1	A0A0U1RQW0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152128

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

230498

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124908

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:

0.000143

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1447936

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

719376

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:

0.000170

Gnomad4 NFE exome

AF:

0.00000633

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74296

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:

0.0000943

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00000831

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

Oct 13, 2023

The c.1204C>T (p.R402C) alteration is located in exon 13 (coding exon 13) of the SEPT7 gene. This alteration results from a C to T substitution at nucleotide position 1204, causing the arginine (R) at amino acid position 402 to be replaced by a cysteine (C). 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

0.25

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

.;T;T;T;T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D;D;D;D

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D

MetaSVM

Uncertain

-0.28

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-7.2

.;.;.;.;D;.

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

.;.;.;.;D;.

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Vest4

0.41

MVP

0.79

MPC

4.0

ClinPred

0.99

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.74

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