chr19-7557242-G-C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM5PP2PP3_StrongPP5_Moderate
The NM_001166114.2(PNPLA6):c.3355G>C(p.Gly1119Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1119?) has been classified as Pathogenic.
Frequency
Consequence
NM_001166114.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PNPLA6 | NM_001166114.2 | c.3355G>C | p.Gly1119Arg | missense_variant | Exon 27 of 32 | ENST00000600737.6 | NP_001159586.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PNPLA6 | ENST00000600737.6 | c.3355G>C | p.Gly1119Arg | missense_variant | Exon 27 of 32 | 1 | NM_001166114.2 | ENSP00000473211.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461140Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726944
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 39 Pathogenic:1
This sequence change replaces glycine with arginine at codon 1081 of the PNPLA6 protein (p.Gly1081Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Oliver McFarlane syndrome and Boucher-Neuhäuser syndrome (PMID: 25574898, 25480986). This variant is also known as p.Gly1129Arg. Experimental studies have shown that this variant affects PNPLA6 protein function (PMID: 25480986). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at