11-66852516-C-G
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_001040716.2(PC):c.1748G>C(p.Arg583Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R583L) has been classified as Pathogenic.
Frequency
Consequence
NM_001040716.2 missense
Scores
Clinical Significance
Conservation
Publications
- pyruvate carboxylase deficiency diseaseInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P
- pyruvate carboxylase deficiency, benign typeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- pyruvate carboxylase deficiency, infantile formInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- pyruvate carboxylase deficiency, severe neonatal typeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PC | NM_001040716.2 | c.1748G>C | p.Arg583Pro | missense_variant | Exon 15 of 23 | ENST00000393960.7 | NP_001035806.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461730Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727156 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at