dbSNP rs537484468: SEPTIN4:p.Arg943Leu (chr17-58521001-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001368771.2(SEPTIN4):c.2828G>T(p.Arg943Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R943C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEPTIN4
NM_001368771.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.93

Publications

0 publications found

Variant links:

Genes affected

SEPTIN4 (HGNC:9165): (septin 4) This gene is a member of the septin 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 highly expressed in brain and heart. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. One of the isoforms (known as ARTS) is distinct; it is localized to the mitochondria, and has a role in apoptosis and cancer. [provided by RefSeq, Nov 2010]

SEPTIN4 links:

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

SEPTIN4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34284818).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368771.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEPTIN4	NM_001368771.2	MANE Select	c.2828G>T	p.Arg943Leu	missense	Exon 12 of 14	NP_001355700.1	O43236-7
SEPTIN4	NM_001256782.2		c.1319G>T	p.Arg440Leu	missense	Exon 11 of 13	NP_001243711.1	O43236-4
SEPTIN4	NM_004574.5		c.1274G>T	p.Arg425Leu	missense	Exon 10 of 12	NP_004565.1	O43236-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEPTIN4	ENST00000672673.2	MANE Select	c.2828G>T	p.Arg943Leu	missense	Exon 12 of 14	ENSP00000500383.1	O43236-7
SEPTIN4	ENST00000317268.7	TSL:1	c.1274G>T	p.Arg425Leu	missense	Exon 10 of 12	ENSP00000321674.3	O43236-1
SEPTIN4	ENST00000317256.10	TSL:1	c.1217G>T	p.Arg406Leu	missense	Exon 10 of 12	ENSP00000321071.6	O43236-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111960

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.038

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.5

PhyloP100

4.9

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.25

Sift

Benign

0.032

Sift4G

Benign

0.21

Polyphen

0.77

Vest4

0.41

MutPred

0.49

Loss of solvent accessibility (P = 0.0079)

MVP

0.82

MPC

1.4

ClinPred

0.97

GERP RS

5.6

Varity_R

0.42

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over