rs201865380
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024589.3(ROGDI):āc.218G>Cā(p.Gly73Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,609,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 33)
Exomes š: 0.0000082 ( 0 hom. )
Consequence
ROGDI
NM_024589.3 missense
NM_024589.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.27
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26787555).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.218G>C | p.Gly73Ala | missense_variant | 4/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.218G>C | p.Gly73Ala | missense_variant | 4/11 | ||
ROGDI | XM_047434636.1 | c.-16+199G>C | intron_variant | ||||
ROGDI | NR_046480.2 | n.262+199G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.218G>C | p.Gly73Ala | missense_variant | 4/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247404Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133860
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GnomAD4 exome AF: 0.00000824 AC: 12AN: 1457060Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 724228
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GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74504
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 73 of the ROGDI protein (p.Gly73Ala). This variant is present in population databases (rs201865380, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ROGDI-related conditions. ClinVar contains an entry for this variant (Variation ID: 580233). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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