7-35801265-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001788.6(SEPTIN7):c.56C>G(p.Thr19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,493,276 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 0.000017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SEPTIN7
NM_001788.6 missense

Scores

Splicing: ADA: 0.002960

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Publications

0 publications found

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-DT (HGNC:51153): (SEPTIN7 divergent transcript)

SEPTIN7-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11907917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 link	c.56C>G	p.Thr19Ser	missense_variant	Exon 1 of 14	ENST00000350320.11	NP_001779.3	Q16181-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEPTIN7	ENST00000350320.11 link	c.56C>G	p.Thr19Ser	missense_variant	Exon 1 of 14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635175.1 link	n.47C>G		non_coding_transcript_exon_variant	Exon 1 of 14	2		ENSP00000489192.1	A0A0U1RQW0
SEPTIN7	ENST00000635047.1 link	c.-243C>G		5_prime_UTR_variant	Exon 1 of 7	4		ENSP00000489480.1	A0A0U1RRE1

Frequencies

GnomAD3 genomes

AF:

0.0000174

AC:

AN:

115068

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:

0.0000362

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1378208

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29292

American (AMR)

AF:

0.0000307

AC:

AN:

32566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24464

East Asian (EAS)

AF:

0.00

AC:

AN:

32304

South Asian (SAS)

AF:

0.00

AC:

AN:

76652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

9.33e-7

AC:

AN:

1072062

Other (OTH)

AF:

0.00

AC:

AN:

57198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000174

AC:

AN:

115068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28914

American (AMR)

AF:

0.00

AC:

AN:

11162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2882

East Asian (EAS)

AF:

0.00

AC:

AN:

3778

South Asian (SAS)

AF:

0.00

AC:

AN:

3070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0000362

AC:

AN:

55300

Other (OTH)

AF:

0.00

AC:

AN:

1480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.56C>G (p.T19S) alteration is located in exon 1 (coding exon 1) of the SEPT7 gene. This alteration results from a C to G substitution at nucleotide position 56, causing the threonine (T) at amino acid position 19 to be replaced by a serine (S). 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

0.061

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.36

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

2.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.19

.;N;.

REVEL

Benign

0.075

Sift

Benign

0.63

.;T;.

Sift4G

Benign

0.81

T;T;D

Polyphen

0.46

.;P;.

Vest4

0.24, 0.39

MutPred

0.37

Loss of glycosylation at T19 (P = 0.0271);Loss of glycosylation at T19 (P = 0.0271);Loss of glycosylation at T19 (P = 0.0271);

MVP

0.64

ClinPred

0.35

GERP RS

3.2

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.21

Mutation Taster

=274/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.036

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over