6-87607759-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_012381.4(ORC3):c.514G>A(p.Val172Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012381.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ORC3 | NM_012381.4 | c.514G>A | p.Val172Ile | missense_variant | 6/20 | ENST00000392844.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ORC3 | ENST00000392844.8 | c.514G>A | p.Val172Ile | missense_variant | 6/20 | 1 | NM_012381.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251236Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135804
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1460090Hom.: 0 Cov.: 29 AF XY: 0.0000220 AC XY: 16AN XY: 726508
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74434
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.514G>A (p.V172I) alteration is located in exon 6 (coding exon 6) of the ORC3 gene. This alteration results from a G to A substitution at nucleotide position 514, causing the valine (V) at amino acid position 172 to be replaced by an isoleucine (I). 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