rs1039568775
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024589.3(ROGDI):c.665dupG(p.Ala223ArgfsTer5) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000197 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G222G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Consequence
ROGDI
NM_024589.3 frameshift
NM_024589.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.85
Publications
0 publications found
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]
ROGDI Gene-Disease associations (from GenCC):
- amelocerebrohypohidrotic syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 16-4797967-G-GC is Pathogenic according to our data. Variant chr16-4797967-G-GC is described in ClinVar as Pathogenic. ClinVar VariationId is 530797.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_024589.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ROGDI | NM_024589.3 | MANE Select | c.665dupG | p.Ala223ArgfsTer5 | frameshift | Exon 9 of 11 | NP_078865.1 | ||
| ROGDI | NR_046480.2 | n.672dupG | non_coding_transcript_exon | Exon 8 of 10 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ROGDI | ENST00000322048.12 | TSL:1 MANE Select | c.665dupG | p.Ala223ArgfsTer5 | frameshift | Exon 9 of 11 | ENSP00000322832.6 | ||
| ROGDI | ENST00000591392.5 | TSL:3 | c.593dupG | p.Ala199ArgfsTer5 | frameshift | Exon 8 of 9 | ENSP00000467509.1 | ||
| ROGDI | ENST00000587711.5 | TSL:5 | c.350dupG | p.Ala118ArgfsTer5 | frameshift | Exon 5 of 6 | ENSP00000467459.1 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152122
Hom.:
Cov.:
33
Gnomad AFR
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GnomAD4 exome Cov.: 37
GnomAD4 exome
Cov.:
37
GnomAD4 genome 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74304 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152122
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74304
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41418
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68008
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
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Allele balance
Age Distribution
Genome Het
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ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Amelocerebrohypohidrotic syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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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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