rs1262969313
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_006047.6(RBM12):c.2532delT(p.Gly845AlafsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
RBM12
NM_006047.6 frameshift
NM_006047.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.865
Publications
3 publications found
Genes affected
RBM12 (HGNC:9898): (RNA binding motif protein 12) This gene encodes a protein that contains several RNA-binding motifs, potential transmembrane domains, and proline-rich regions. This gene and the gene for copine I overlap at map location 20q11.21. Alternative splicing in the 5' UTR results in four transcript variants. All variants encode the same protein. [provided by RefSeq, Nov 2010]
CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0954 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 20-35652790-CA-C is Pathogenic according to our data. Variant chr20-35652790-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 433196.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RBM12 | ENST00000374114.8 | c.2532delT | p.Gly845AlafsTer13 | frameshift_variant | Exon 3 of 3 | 1 | NM_006047.6 | ENSP00000363228.3 | ||
| CPNE1 | ENST00000397443.7 | c.-1+11969delT | intron_variant | Intron 1 of 15 | 5 | NM_152925.3 | ENSP00000380585.1 | |||
| CPNE1 | ENST00000437340.5 | c.-1+12011delT | intron_variant | Intron 1 of 15 | 1 | ENSP00000415597.1 | ||||
| ENSG00000272897 | ENST00000541176.2 | n.*32+2411delT | intron_variant | Intron 6 of 8 | 2 | ENSP00000443983.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1457358Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724732 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1457358
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
724732
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33242
American (AMR)
AF:
AC:
0
AN:
44174
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
25728
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
0
AN:
85818
European-Finnish (FIN)
AF:
AC:
1
AN:
53258
Middle Eastern (MID)
AF:
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109570
Other (OTH)
AF:
AC:
0
AN:
60158
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Schizophrenia 19 Pathogenic:1
Aug 17, 2017
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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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