rs1432426676

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002688.6(SEPTIN5):c.35C>A(p.Ala12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,355,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A12V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SEPTIN5
NM_002688.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.756

Publications

0 publications found

Variant links:

Genes affected

SEPTIN5 (HGNC:9164): (septin 5) This gene is a member of the septin gene family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is mapped to 22q11, the region frequently deleted in DiGeorge and velocardiofacial syndromes. A translocation involving the MLL gene and this gene has also been reported in patients with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. The presence of a non-consensus polyA signal (AACAAT) in this gene also results in read-through transcription into the downstream neighboring gene (GP1BB; platelet glycoprotein Ib), whereby larger, non-coding transcripts are produced. [provided by RefSeq, Dec 2010]

SEPTIN5 links:

ENSG00000304096 (HGNC:):

ENSG00000304096 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=0.13528779).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002688.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN5	NM_002688.6	MANE Select	c.35C>A	p.Ala12Glu	missense	Exon 1 of 12	NP_002679.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEPTIN5	ENST00000455784.7	TSL:1 MANE Select	c.35C>A	p.Ala12Glu	missense	Exon 1 of 12	ENSP00000391311.2	Q99719-1
SEPTIN5	ENST00000942371.1		c.35C>A	p.Ala12Glu	missense	Exon 1 of 12	ENSP00000612430.1
SEPTIN5	ENST00000406395.5	TSL:5	c.35C>A	p.Ala12Glu	missense	Exon 1 of 12	ENSP00000384535.1	E7EX32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000221

AC:

AN:

1355714

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

669030

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:

27634

American (AMR)

AF:

0.00

AC:

AN:

33006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23940

East Asian (EAS)

AF:

0.00

AC:

AN:

32546

South Asian (SAS)

AF:

0.00

AC:

AN:

76516

European-Finnish (FIN)

AF:

0.0000279

AC:

AN:

35882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4220

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1065656

Other (OTH)

AF:

0.00

AC:

AN:

56314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0556734), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.10

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

0.76

PROVEAN

Benign

0.0

REVEL

Benign

0.019

Sift

Benign

0.80

Sift4G

Benign

0.48

Polyphen

0.017

Vest4

0.16

MutPred

0.42

Gain of sheet (P = 0.0166)

MVP

0.33

MPC

1.2

ClinPred

0.063

GERP RS

0.86

PromoterAI

-0.044

Neutral

(source)

Varity_R

0.088

gMVP

0.70

Mutation Taster

=88/12

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over