rs1555741826
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020719.3(PRR12):c.4502_4505del(p.Leu1501ArgfsTer146) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
PRR12
NM_020719.3 frameshift
NM_020719.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
PRR12 (HGNC:29217): (proline rich 12) This gene encodes a proline-rich protein that contains two A-T hook DNA binding domains. A chromosomal translocation and gene fusion between this gene and zinc finger, MIZ-type containing 1 (Gene ID: 57178) may underlie intellectual disability and neuropsychiatric problems in a human patient. Enriched expression of this gene in embryonic mouse brain suggests that this gene may play a role in nervous system development. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-49601645-GCTGC-G is Pathogenic according to our data. Variant chr19-49601645-GCTGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 446255.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-49601645-GCTGC-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRR12 | NM_020719.3 | c.4502_4505del | p.Leu1501ArgfsTer146 | frameshift_variant | 6/14 | ENST00000418929.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRR12 | ENST00000418929.7 | c.4502_4505del | p.Leu1501ArgfsTer146 | frameshift_variant | 6/14 | 5 | NM_020719.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neuroocular syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 30, 2024 | - - |
Autism;C0240063:Iris coloboma;C0454644:Delayed speech and language development;C1854301:Motor delay;C4025846:Abnormality of vision Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 15, 2017 | This variant was seen once in our laboratory de novo in a 8-year-old male with delayed motor milestones, delayed speech, intellectual disability, hypotonia, unilateral sensorineural hearing loss, dysmorphic features (downslanting palpebral fissures, ptosis, mid-face hypoplasia, low set ears), short stature, eye anomalies (esotropia, stellate iris, distichiasis), vision loss, and skeletal abnormalities (scapular winging). - |
Computational scores
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Calibrated prediction
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Prediction
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