rs148051351
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_024589.3(ROGDI):c.243C>T(p.Ala81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,607,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
ROGDI
NM_024589.3 synonymous
NM_024589.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.36
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 16-4801279-G-A is Benign according to our data. Variant chr16-4801279-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 241506.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=1}.
BP7
?
Synonymous conserved (PhyloP=-2.36 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.243C>T | p.Ala81= | synonymous_variant | 4/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.243C>T | p.Ala81= | synonymous_variant | 4/11 | ||
ROGDI | XM_047434636.1 | c.-16+224C>T | intron_variant | ||||
ROGDI | NR_046480.2 | n.262+224C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.243C>T | p.Ala81= | synonymous_variant | 4/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000677 AC: 103AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000236 AC: 58AN: 246226Hom.: 0 AF XY: 0.000210 AC XY: 28AN XY: 133234
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GnomAD4 exome AF: 0.000101 AC: 147AN: 1455622Hom.: 1 Cov.: 31 AF XY: 0.0000871 AC XY: 63AN XY: 723450
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GnomAD4 genome ? AF: 0.000683 AC: 104AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40AN XY: 74458
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
ROGDI-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 14, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at