dbSNP rs547978971: SEPTIN7:p.Ser2* (chr7-35801214-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_001788.6(SEPTIN7):c.5C>A(p.Ser2*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,365,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SEPTIN7
NM_001788.6 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.996 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6 link	c.5C>A	p.Ser2*	stop_gained	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.5C>A	p.Ser2*	stop_gained	Exon 1 of 14	5	NM_001788.6	ENSP00000344868.8	Q16181-1E7EPK1
SEPTIN7	ENST00000635047.1 link	c.-294C>A		upstream_gene_variant		4		ENSP00000489480.1	A0A0U1RRE1
SEPTIN7	ENST00000635175.1 link	n.-5C>A		upstream_gene_variant		2		ENSP00000489192.1	A0A0U1RQW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000293

AC:

AN:

1365482

Hom.:

Cov.:

AF XY:

0.00000446

AC XY:

AN XY:

672444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28836

American (AMR)

AF:

0.00

AC:

AN:

31410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24216

East Asian (EAS)

AF:

0.00

AC:

AN:

31382

South Asian (SAS)

AF:

0.00

AC:

AN:

75816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4450

European-Non Finnish (NFE)

AF:

0.00000376

AC:

AN:

1064072

Other (OTH)

AF:

0.00

AC:

AN:

56550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Benign

0.44

PhyloP100

3.4

Vest4

0.64, 0.66

GERP RS

3.6

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=10/190

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs547978971

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