rs1555491350
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024589.3(ROGDI):c.340C>T(p.Gln114Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
ROGDI
NM_024589.3 stop_gained
NM_024589.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.96
Genes affected
ROGDI (HGNC:29478): (rogdi atypical leucine zipper) Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 16-4799778-G-A is Pathogenic according to our data. Variant chr16-4799778-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 461607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.340C>T | p.Gln114Ter | stop_gained | 6/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.340C>T | p.Gln114Ter | stop_gained | 6/11 | ||
ROGDI | XM_047434636.1 | c.70C>T | p.Gln24Ter | stop_gained | 4/9 | ||
ROGDI | NR_046480.2 | n.347C>T | non_coding_transcript_exon_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.340C>T | p.Gln114Ter | stop_gained | 6/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 07, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2019 | This variant has not been reported in the literature in individuals with ROGDI-related disease. ClinVar contains an entry for this variant (Variation ID: 461607). This sequence change creates a premature translational stop signal (p.Gln114*) in the ROGDI gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Loss-of-function variants in ROGDI are known to be pathogenic (PMID: 22424600, 23086778). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
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