dbSNP rs1432426676: SEPTIN5:p.Ala12Glu (chr22-19714623-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.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. 14/20 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: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SEPTIN5
NM_002688.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.756

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:

LOC124905079 (HGNC:):

LOC124905079 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=0.13528779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN5	NM_002688.6 link	c.35C>A	p.Ala12Glu	missense_variant	Exon 1 of 12	ENST00000455784.7	NP_002679.2	Q99719-1X5DNA9
LOC124905079	XR_007068003.1 link	n.99+74G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEPTIN5	ENST00000455784.7 link	c.35C>A	p.Ala12Glu	missense_variant	Exon 1 of 12	1	NM_002688.6	ENSP00000391311.2	Q99719-1
SEPTIN5	ENST00000406395.5 link	c.35C>A	p.Ala12Glu	missense_variant	Exon 1 of 12	5		ENSP00000384535.1	E7EX32
SEPTIN5	ENST00000406172.6 link	n.35C>A		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000385356.2	E7EQM7
SEPTIN5	ENST00000412544.5 link	c.-256C>A		upstream_gene_variant		5		ENSP00000408678.1	C9JM82

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000279

Gnomad4 NFE exome

AF:

0.00000188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.019

Sift

Benign

0.80

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.017

B;.

Vest4

0.16

MutPred

0.42

Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);

MVP

0.33

MPC

1.2

ClinPred

0.063

GERP RS

0.86

Varity_R

0.088

gMVP

0.70

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over