chr16-4797495-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024589.3(ROGDI):c.829G>A(p.Val277Met) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,084 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V277L) has been classified as Uncertain significance.
Frequency
Consequence
NM_024589.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.829G>A | p.Val277Met | missense_variant | 11/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.850G>A | p.Val284Met | missense_variant | 11/11 | ||
ROGDI | XM_047434636.1 | c.580G>A | p.Val194Met | missense_variant | 9/9 | ||
ROGDI | NR_046480.2 | n.836G>A | non_coding_transcript_exon_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.829G>A | p.Val277Met | missense_variant | 11/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248186Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134500
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460976Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726816
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74288
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.829G>A (p.V277M) alteration is located in exon 11 (coding exon 11) of the ROGDI gene. This alteration results from a G to A substitution at nucleotide position 829, causing the valine (V) at amino acid position 277 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 15, 2018 | - - |
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 277 of the ROGDI protein (p.Val277Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 586408). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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