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GeneBe

22-41986065-G-A

Variant summary

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

The NM_001363845.2(SEPTIN3):c.1778G>A(p.Arg593Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SEPTIN3
NM_001363845.2 missense

Scores

1
3
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71
Variant links:
Genes affected
SEPTIN3 (HGNC:10750): (septin 3) This gene belongs to the septin family of GTPases. Members of this family are required for cytokinesis. Expression is upregulated by retinoic acid in a human teratocarcinoma cell line. The specific function of this gene has not been determined. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2018]

Genome browser will be placed here

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=0.15421167).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEPTIN3NM_001363845.2 linkuse as main transcriptc.1778G>A p.Arg593Gln missense_variant 4/12 ENST00000644076.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEPTIN3ENST00000644076.2 linkuse as main transcriptc.1778G>A p.Arg593Gln missense_variant 4/12 NM_001363845.2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251230
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461454
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727014
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 09, 2024The c.284G>A (p.R95Q) alteration is located in exon 3 (coding exon 3) of the SEPT3 gene. This alteration results from a G to A substitution at nucleotide position 284, causing the arginine (R) at amino acid position 95 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
Cadd
Pathogenic
27
Dann
Pathogenic
1.0
Eigen
Benign
-0.092
Eigen_PC
Benign
0.056
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.50
T
Polyphen
0.022, 0.090, 0.017
.;.;B;B;B
Vest4
0.45, 0.40, 0.40
MVP
0.62
MPC
1.3
ClinPred
0.40
T
GERP RS
3.7
Varity_R
0.23
gMVP
0.83

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

LitVar

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

Other links and lift over

dbSNP: rs200659820; hg19: chr22-42382069; API