Genetic Variant NM_001788.6:c.20C>T (chr7-35801229-C-T) – 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.20C>T(p.Ser7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,381,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

SEPTIN7
NM_001788.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

2 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:

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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=0.2337986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 link	c.20C>T	p.Ser7Phe	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.20C>T	p.Ser7Phe	missense_variant	Exon 1 of 14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635175.1 link	n.11C>T		non_coding_transcript_exon_variant	Exon 1 of 14	2		ENSP00000489192.1	A0A0U1RQW0
SEPTIN7	ENST00000635047.1 link	c.-279C>T		5_prime_UTR_variant	Exon 1 of 7	4		ENSP00000489480.1	A0A0U1RRE1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000705

AC:

AN:

141752

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000174

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000868

AC:

AN:

1381752

Hom.:

Cov.:

AF XY:

0.00000880

AC XY:

AN XY:

681642

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29702

American (AMR)

AF:

0.0000299

AC:

AN:

33404

Ashkenazi Jewish (ASJ)

AF:

0.0000408

AC:

AN:

24538

East Asian (EAS)

AF:

0.00

AC:

AN:

32876

South Asian (SAS)

AF:

0.00

AC:

AN:

77152

European-Finnish (FIN)

AF:

0.0000204

AC:

AN:

49104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4586

European-Non Finnish (NFE)

AF:

0.00000839

AC:

AN:

1073104

Other (OTH)

AF:

0.00

AC:

AN:

57286

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;T

Eigen

Benign

0.048

Eigen_PC

Benign

0.073

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.80

T;T;T

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.96

PhyloP100

1.3

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.1

.;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.025

.;D;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.68

.;P;.

Vest4

0.29, 0.45

MutPred

0.35

Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);

MVP

0.59

ClinPred

0.68

GERP RS

3.0

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

gMVP

0.26

Mutation Taster

=80/20

polymorphism

(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

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NM_001788.6:c.20C>T

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