chr7-35801214-C-T

Position:

chr7-35801214-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001788.6(SEPTIN7):c.5C>T(p.Ser2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000494 in 1,517,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

SEPTIN7
NM_001788.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.36

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 2 ACMG points.

PM1

In a modified_residue N-acetylserine (size 0) in uniprot entity SEPT7_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18528733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 linkuse as main transcript	c.5C>T	p.Ser2Leu	missense_variant	1/14	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.5C>T	p.Ser2Leu	missense_variant	1/14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635047.1 linkuse as main transcript	c.-294C>T		upstream_gene_variant		4		ENSP00000489480.1	A0A0U1RRE1
SEPTIN7	ENST00000635175.1 linkuse as main transcript	n.-5C>T		upstream_gene_variant		2		ENSP00000489192.1	A0A0U1RQW0

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151960

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

129716

Hom.:

AF XY:

0.0000566

AC XY:

AN XY:

70718

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:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1365480

Hom.:

Cov.:

AF XY:

0.0000520

AC XY:

AN XY:

672444

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:

0.00

Gnomad4 NFE exome

AF:

0.0000667

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000967

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000265

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

Jul 02, 2024

The c.5C>T (p.S2L) alteration is located in exon 1 (coding exon 1) of the SEPT7 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a leucine (L). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.87

D;D;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.89

.;N;.

REVEL

Benign

0.057

Sift

Uncertain

0.017

.;D;.

Sift4G

Uncertain

0.010

D;T;D

Polyphen

0.029

.;B;.

Vest4

0.46, 0.41

MutPred

0.27

Loss of phosphorylation at S2 (P = 0.0064);Loss of phosphorylation at S2 (P = 0.0064);Loss of phosphorylation at S2 (P = 0.0064);

MVP

0.46

ClinPred

0.24

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.23

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