chr12-112870007-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate
The NM_001143854.2(RPH3A):c.764G>C(p.Gly255Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. G255R) has been classified as Pathogenic.
Frequency
Consequence
NM_001143854.2 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 |
---|---|---|---|---|---|---|---|
RPH3A | NM_001143854.2 | c.764G>C | p.Gly255Ala | missense_variant | 10/22 | ENST00000389385.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPH3A | ENST00000389385.9 | c.764G>C | p.Gly255Ala | missense_variant | 10/22 | 1 | NM_001143854.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000195 AC: 49AN: 250888Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135762
GnomAD4 exome AF: 0.000111 AC: 162AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 88AN XY: 727242
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74438
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.764G>C (p.G255A) alteration is located in exon 10 (coding exon 8) of the RPH3A gene. This alteration results from a G to C substitution at nucleotide position 764, causing the glycine (G) at amino acid position 255 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at