rs140825810
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001166114.2(PNPLA6):āc.171A>Cā(p.Gly57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,585,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00046 ( 0 hom., cov: 32)
Exomes š: 0.000061 ( 0 hom. )
Consequence
PNPLA6
NM_001166114.2 synonymous
NM_001166114.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.280
Genes affected
PNPLA6 (HGNC:16268): (patatin like phospholipase domain containing 6) This gene encodes a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells. Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 19-7535959-A-C is Benign according to our data. Variant chr19-7535959-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 469623.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BP7
?
Synonymous conserved (PhyloP=0.28 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA6 | NM_001166114.2 | c.171A>C | p.Gly57= | synonymous_variant | 1/32 | ENST00000600737.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA6 | ENST00000600737.6 | c.171A>C | p.Gly57= | synonymous_variant | 1/32 | 1 | NM_001166114.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 151994Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
66
AN:
151994
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000169 AC: 35AN: 206524Hom.: 0 AF XY: 0.0000986 AC XY: 11AN XY: 111592
GnomAD3 exomes
AF:
AC:
35
AN:
206524
Hom.:
AF XY:
AC XY:
11
AN XY:
111592
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000614 AC: 88AN: 1433058Hom.: 0 Cov.: 32 AF XY: 0.0000450 AC XY: 32AN XY: 710920
GnomAD4 exome
AF:
AC:
88
AN:
1433058
Hom.:
Cov.:
32
AF XY:
AC XY:
32
AN XY:
710920
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000460 AC: 70AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74372
GnomAD4 genome
?
AF:
AC:
70
AN:
152112
Hom.:
Cov.:
32
AF XY:
AC XY:
30
AN XY:
74372
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 17, 2017 | - - |
Hereditary spastic paraplegia 39 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at