rs199696526
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_144605.5(SEPTIN12):c.266C>T(p.Thr89Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
SEPTIN12
NM_144605.5 missense
NM_144605.5 missense
Scores
11
5
2
Clinical Significance
Conservation
PhyloP100: 9.91
Genes affected
SEPTIN12 (HGNC:26348): (septin 12) This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM1
?
In a binding_site (size 0) in uniprot entity SEP12_HUMAN
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.89
BS2
?
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEPTIN12 | NM_144605.5 | c.266C>T | p.Thr89Met | missense_variant | 3/10 | ENST00000268231.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPTIN12 | ENST00000268231.13 | c.266C>T | p.Thr89Met | missense_variant | 3/10 | 1 | NM_144605.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152038Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 250174Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135342
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461508Hom.: 0 Cov.: 38 AF XY: 0.0000289 AC XY: 21AN XY: 726990
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74394
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ClinVar
Significance: risk factor
Submissions summary: Other:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spermatogenic failure 10 Other:2
risk factor, no assertion criteria provided | literature only | OMIM | Apr 01, 2012 | - - |
not provided, no classification provided | literature only | Reproductive Endocrinology and immunology College of Medicine, National Cheng Kung University | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.17
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at