rs61744333
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001113491.2(SEPTIN9):c.201C>T(p.Gly67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,790 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0029 ( 4 hom. )
Consequence
SEPTIN9
NM_001113491.2 synonymous
NM_001113491.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.50
Genes affected
SEPTIN9 (HGNC:7323): (septin 9) This gene is a member of the septin family involved in cytokinesis and cell cycle control. This gene is a candidate for the ovarian tumor suppressor gene. Mutations in this gene cause hereditary neuralgic amyotrophy, also known as neuritis with brachial predilection. A chromosomal translocation involving this gene on chromosome 17 and the MLL gene on chromosome 11 results in acute myelomonocytic leukemia. Multiple alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
Variant 17-77402183-C-T is Benign according to our data. Variant chr17-77402183-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 325539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-77402183-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.5 with no splicing effect.
BS2
?
High AC in GnomAd4 at 326 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEPTIN9 | NM_001113491.2 | c.201C>T | p.Gly67= | synonymous_variant | 3/12 | ENST00000427177.6 | |
SEPTIN9 | NM_006640.5 | c.147C>T | p.Gly49= | synonymous_variant | 2/11 | ENST00000329047.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPTIN9 | ENST00000427177.6 | c.201C>T | p.Gly67= | synonymous_variant | 3/12 | 1 | NM_001113491.2 | A1 | |
SEPTIN9 | ENST00000329047.13 | c.147C>T | p.Gly49= | synonymous_variant | 2/11 | 1 | NM_006640.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00214 AC: 325AN: 152122Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00202 AC: 503AN: 248798Hom.: 0 AF XY: 0.00210 AC XY: 284AN XY: 135112
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GnomAD4 exome AF: 0.00288 AC: 4213AN: 1461550Hom.: 4 Cov.: 32 AF XY: 0.00290 AC XY: 2111AN XY: 727060
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GnomAD4 genome ? AF: 0.00214 AC: 326AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00206 AC XY: 153AN XY: 74432
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | SEPTIN9: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 20, 2016 | - - |
Amyotrophic neuralgia Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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