rs987191768
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024589.3(ROGDI):āc.397A>Gā(p.Ser133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_024589.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.397A>G | p.Ser133Gly | missense_variant | 6/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.397A>G | p.Ser133Gly | missense_variant | 6/11 | ||
ROGDI | XM_047434636.1 | c.127A>G | p.Ser43Gly | missense_variant | 4/9 | ||
ROGDI | NR_046480.2 | n.404A>G | non_coding_transcript_exon_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.397A>G | p.Ser133Gly | missense_variant | 6/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152094Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250656Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135568
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461486Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727048
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152094Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74288
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | The c.397A>G (p.S133G) alteration is located in exon 6 (coding exon 6) of the ROGDI gene. This alteration results from a A to G substitution at nucleotide position 397, causing the serine (S) at amino acid position 133 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2022 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 133 of the ROGDI protein (p.Ser133Gly). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 410629). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at