chr22-38135048-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PP5_ModerateBP4
The NM_003560.4(PLA2G6):c.834G>C(p.Gln278His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PLA2G6
NM_003560.4 missense
NM_003560.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 4.23
Genes affected
PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_003560.4
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-38135048-C-G is Pathogenic according to our data. Variant chr22-38135048-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 522674.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.31157464). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLA2G6 | NM_003560.4 | c.834G>C | p.Gln278His | missense_variant | 6/17 | ENST00000332509.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLA2G6 | ENST00000332509.8 | c.834G>C | p.Gln278His | missense_variant | 6/17 | 1 | NM_003560.4 | P3 | |
ENST00000624072.1 | n.4833C>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Infantile neuroaxonal dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;D;D;.
REVEL
Benign
Sift
Benign
T;T;T;.
Sift4G
Benign
T;T;T;T
Polyphen
D;D;D;.
Vest4
MutPred
Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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