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GeneBe

22-41989680-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001363845.2(SEPTIN3):c.2159A>G(p.Gln720Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SEPTIN3
NM_001363845.2 missense

Scores

1
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.29
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEPTIN3NM_001363845.2 linkuse as main transcriptc.2159A>G p.Gln720Arg missense_variant 7/12 ENST00000644076.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEPTIN3ENST00000644076.2 linkuse as main transcriptc.2159A>G p.Gln720Arg missense_variant 7/12 NM_001363845.2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

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 GeneticsSep 14, 2023The c.665A>G (p.Q222R) alteration is located in exon 6 (coding exon 6) of the SEPT3 gene. This alteration results from a A to G substitution at nucleotide position 665, causing the glutamine (Q) at amino acid position 222 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
Cadd
Uncertain
24
Dann
Uncertain
1.0
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.75
T
Polyphen
0.98, 0.0040, 0.98
.;D;B;D
Vest4
0.62, 0.63, 0.63
MVP
0.60
MPC
2.0
ClinPred
0.95
D
GERP RS
5.2
Varity_R
0.68
gMVP
0.71

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.

Other links and lift over

dbSNP: rs2078271459; hg19: chr22-42385684; API