dbSNP rs2710800: SEPTIN7:p.Phe404Leu (chr7-35903153-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001788.6(SEPTIN7):c.1212C>A(p.Phe404Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F404F) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEPTIN7
NM_001788.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

3 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:

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=0.18829423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 link	c.1212C>A	p.Phe404Leu	missense_variant	Exon 13 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.1212C>A	p.Phe404Leu	missense_variant	Exon 13 of 14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635175.1 link	n.*1129C>A		non_coding_transcript_exon_variant	Exon 13 of 14	2		ENSP00000489192.1	A0A0U1RQW0
SEPTIN7	ENST00000635175.1 link	n.*1129C>A		3_prime_UTR_variant	Exon 13 of 14	2		ENSP00000489192.1	A0A0U1RQW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.93e-7

AC:

AN:

1443778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717874

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

38964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25928

East Asian (EAS)

AF:

0.00

AC:

AN:

39146

South Asian (SAS)

AF:

0.00

AC:

AN:

84332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103420

Other (OTH)

AF:

0.00

AC:

AN:

59900

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.068

.;T;T;T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

2.7

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.4

.;.;.;.;D;.

REVEL

Benign

0.27

Sift

Benign

0.27

.;.;.;.;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T

Vest4

0.61

MutPred

0.26

.;Gain of MoRF binding (P = 0.1327);.;.;.;.;

MVP

0.82

MPC

2.1

ClinPred

0.75

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.72

Mutation Taster

=44/56

disease causing

(source)

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

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

rs2710800

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over