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GeneBe

22-41987267-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001363845.2(SEPTIN3):c.1887C>G(p.Asp629Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEPTIN3
NM_001363845.2 missense

Scores

4
2
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEPTIN3NM_001363845.2 linkuse as main transcriptc.1887C>G p.Asp629Glu missense_variant 5/12 ENST00000644076.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEPTIN3ENST00000644076.2 linkuse as main transcriptc.1887C>G p.Asp629Glu missense_variant 5/12 NM_001363845.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsOct 26, 2023The c.393C>G (p.D131E) alteration is located in exon 4 (coding exon 4) of the SEPT3 gene. This alteration results from a C to G substitution at nucleotide position 393, causing the aspartic acid (D) at amino acid position 131 to be replaced by a glutamic acid (E). 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
Pathogenic
0.97
BayesDel_addAF
Benign
-0.0042
T
BayesDel_noAF
Benign
-0.24
Cadd
Uncertain
23
Dann
Uncertain
1.0
Eigen
Benign
0.097
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.92
D;D;D;D;D
MetaSVM
Benign
-0.44
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.87
D
Polyphen
0.049, 0.99, 0.040
.;.;B;D;B
Vest4
0.75, 0.75, 0.75
MutPred
0.91
.;.;Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);
MVP
0.80
MPC
1.8
ClinPred
0.99
D
GERP RS
4.3
Varity_R
0.87
gMVP
0.90

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.

Other links and lift over

hg19: chr22-42383271; API