22-19722938-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000431044.5(ENSG00000284874):n.*454G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 441,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
ENSG00000284874
ENST00000431044.5 non_coding_transcript_exon
ENST00000431044.5 non_coding_transcript_exon
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0380
Publications
1 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SEPTIN5 | NM_002688.6 | c.*454G>A | 3_prime_UTR_variant | Exon 12 of 12 | ENST00000455784.7 | NP_002679.2 | ||
| SEPT5-GP1BB | NR_037611.1 | n.3109G>A | non_coding_transcript_exon_variant | Exon 11 of 12 | ||||
| SEPT5-GP1BB | NR_037612.1 | n.1613G>A | non_coding_transcript_exon_variant | Exon 11 of 12 | ||||
| SEPTIN5 | NM_001009939.3 | c.*539G>A | 3_prime_UTR_variant | Exon 11 of 11 | NP_001009939.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ENSG00000284874 | ENST00000455843.5 | n.*454G>A | non_coding_transcript_exon_variant | Exon 11 of 12 | 1 | ENSP00000391731.1 | ||||
| SEPTIN5 | ENST00000455784.7 | c.*454G>A | 3_prime_UTR_variant | Exon 12 of 12 | 1 | NM_002688.6 | ENSP00000391311.2 | |||
| ENSG00000284874 | ENST00000455843.5 | n.*454G>A | 3_prime_UTR_variant | Exon 11 of 12 | 1 | ENSP00000391731.1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152210
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000242 AC: 7AN: 289568Hom.: 0 Cov.: 0 AF XY: 0.00000662 AC XY: 1AN XY: 151036 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
289568
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
151036
show subpopulations
African (AFR)
AF:
AC:
1
AN:
9436
American (AMR)
AF:
AC:
0
AN:
13824
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
9930
East Asian (EAS)
AF:
AC:
0
AN:
19746
South Asian (SAS)
AF:
AC:
0
AN:
42896
European-Finnish (FIN)
AF:
AC:
0
AN:
9280
Middle Eastern (MID)
AF:
AC:
0
AN:
1200
European-Non Finnish (NFE)
AF:
AC:
6
AN:
166350
Other (OTH)
AF:
AC:
0
AN:
16906
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.432
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
152210
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74368
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41460
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2088
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
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
Publications
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