chr22-19720439-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002688.6(SEPTIN5):āc.482C>Gā(p.Ser161Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
SEPTIN5
NM_002688.6 missense
NM_002688.6 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 7.80
Genes affected
SEPTIN5 (HGNC:9164): (septin 5) This gene is a member of the septin gene 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 mapped to 22q11, the region frequently deleted in DiGeorge and velocardiofacial syndromes. A translocation involving the MLL gene and this gene has also been reported in patients with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. The presence of a non-consensus polyA signal (AACAAT) in this gene also results in read-through transcription into the downstream neighboring gene (GP1BB; platelet glycoprotein Ib), whereby larger, non-coding transcripts are produced. [provided by RefSeq, Dec 2010]
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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 |
---|---|---|---|---|---|---|---|
SEPTIN5 | NM_002688.6 | c.482C>G | p.Ser161Cys | missense_variant | 6/12 | ENST00000455784.7 | |
SEPT5-GP1BB | NR_037611.1 | n.2027C>G | non_coding_transcript_exon_variant | 5/12 | |||
SEPTIN5 | NM_001009939.3 | c.509C>G | p.Ser170Cys | missense_variant | 5/11 | ||
SEPT5-GP1BB | NR_037612.1 | n.531C>G | non_coding_transcript_exon_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPTIN5 | ENST00000455784.7 | c.482C>G | p.Ser161Cys | missense_variant | 6/12 | 1 | NM_002688.6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250716Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135768
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461520Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727058
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ExAC
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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 submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.482C>G (p.S161C) alteration is located in exon 6 (coding exon 6) of the SEPT5 gene. This alteration results from a C to G substitution at nucleotide position 482, causing the serine (S) at amino acid position 161 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D
PROVEAN
Uncertain
D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;T;D;D;T
Polyphen
D;.;.;.;.;.;.
Vest4
MutPred
Loss of glycosylation at S161 (P = 0.2857);Loss of glycosylation at S161 (P = 0.2857);.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at