7-35879848-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001788.6(SEPTIN7):c.538A>G(p.Met180Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,438,748 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: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

SEPTIN7
NM_001788.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Publications

1 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 link	c.538A>G	p.Met180Val	missense_variant	Exon 7 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.538A>G	p.Met180Val	missense_variant	Exon 7 of 14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635047.1 link	c.379A>G	p.Met127Val	missense_variant	Exon 7 of 7	4		ENSP00000489480.1	A0A0U1RRE1
SEPTIN7	ENST00000635175.1 link	n.*455A>G		non_coding_transcript_exon_variant	Exon 7 of 14	2		ENSP00000489192.1	A0A0U1RQW0
SEPTIN7	ENST00000635175.1 link	n.*455A>G		3_prime_UTR_variant	Exon 7 of 14	2		ENSP00000489192.1	A0A0U1RQW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000901

AC:

AN:

221882

AF XY:

0.0000168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000633

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

1438748

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

713826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33076

American (AMR)

AF:

0.0000952

AC:

AN:

42028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25670

East Asian (EAS)

AF:

0.00

AC:

AN:

39162

South Asian (SAS)

AF:

0.00

AC:

AN:

82684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1098384

Other (OTH)

AF:

0.00

AC:

AN:

59610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.538A>G (p.M180V) alteration is located in exon 7 (coding exon 7) of the SEPT7 gene. This alteration results from a A to G substitution at nucleotide position 538, causing the methionine (M) at amino acid position 180 to be replaced by a valine (V). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T;T;T;.;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;D;D;D;D;D

M_CAP

Uncertain

0.094

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D

MetaSVM

Uncertain

0.14

PhyloP100

9.3

PrimateAI

Pathogenic

0.88

REVEL

Uncertain

0.55

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Vest4

0.82

MutPred

0.80

.;Gain of methylation at K181 (P = 0.0386);.;.;.;.;

MVP

0.77

MPC

1.3

ClinPred

0.99

GERP RS

5.5

gMVP

0.91

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.

7-35879848-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over