dbSNP rs1387019746: SEPTIN5:p.Leu89Ile (chr22-19720141-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002688.6(SEPTIN5):c.265C>A(p.Leu89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign 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: 6.8e-7 ( 0 hom. )

Consequence

SEPTIN5
NM_002688.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.180

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:

ENSG00000284874 (HGNC:):

ENSG00000284874 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103491575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN5	NM_002688.6 link	c.265C>A	p.Leu89Ile	missense_variant	Exon 5 of 12	ENST00000455784.7	NP_002679.2	Q99719-1X5DNA9
SEPTIN5	NM_001009939.3 link	c.292C>A	p.Leu98Ile	missense_variant	Exon 4 of 11		NP_001009939.1	Q99719-2
SEPT5-GP1BB	NR_037611.1 link	n.1810C>A		non_coding_transcript_exon_variant	Exon 4 of 12
SEPT5-GP1BB	NR_037612.1 link	n.314C>A		non_coding_transcript_exon_variant	Exon 4 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN5	ENST00000455784.7 link	c.265C>A	p.Leu89Ile	missense_variant	Exon 5 of 12	1	NM_002688.6	ENSP00000391311.2		Q99719-1
ENSG00000284874	ENST00000455843.5 link	n.292C>A		non_coding_transcript_exon_variant	Exon 4 of 12	1		ENSP00000391731.1		G3XAH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250222

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

6.84e-7

AC:

AN:

1460944

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.097

T;.;T;T;T;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.82

T;T;T;T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.10

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.26

N;.;.;.;.;.;.

PROVEAN

Benign

0.11

N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.043

D;T;D;T;T;T;D

Sift4G

Benign

0.14

T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.;.

Vest4

0.24

MutPred

0.42

Gain of catalytic residue at L89 (P = 0.062);Gain of catalytic residue at L89 (P = 0.062);.;.;.;.;.;

MVP

0.56

MPC

1.1

ClinPred

0.093

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over