rs747956857

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001031689.3(PLAA):​c.68G>T​(p.Gly23Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,344 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PLAA
NM_001031689.3 missense

Scores

7
9
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.63
Variant links:
Genes affected
PLAA (HGNC:9043): (phospholipase A2 activating protein) Predicted to enable ubiquitin binding activity. Involved in cellular response to lipopolysaccharide; macroautophagy; and positive regulation of phospholipase A2 activity. Located in cytoplasm; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
IFT74 (HGNC:21424): (intraflagellar transport 74) This gene encodes a core intraflagellar transport (IFT) protein which belongs to a multi-protein complex involved in the transport of ciliary proteins along axonemal microtubules. IFT proteins are found at the base of the cilium as well as inside the cilium, where they assemble into long arrays between the ciliary base and tip. This protein, together with intraflagellar transport protein 81, binds and transports tubulin within cilia and is required for ciliogenesis. Naturally occurring mutations in this gene are associated with amyotrophic lateral sclerosis--frontotemporal dementia and Bardet-Biedl Syndrome. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.847
PP5
Variant 9-26946978-C-A is Pathogenic according to our data. Variant chr9-26946978-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 427941.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLAANM_001031689.3 linkc.68G>T p.Gly23Val missense_variant Exon 1 of 14 ENST00000397292.8 NP_001026859.1 Q9Y263

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLAAENST00000397292.8 linkc.68G>T p.Gly23Val missense_variant Exon 1 of 14 1 NM_001031689.3 ENSP00000380460.3 Q9Y263

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1440344
Hom.:
0
Cov.:
31
AF XY:
0.00000140
AC XY:
1
AN XY:
714618
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.07e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000829
AC:
1

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies Pathogenic:1
Jun 21, 2017
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.5
N;N
REVEL
Uncertain
0.40
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.027
D;D
Polyphen
0.99
D;D
Vest4
0.92
MutPred
0.47
Loss of disorder (P = 0.2009);Loss of disorder (P = 0.2009);
MVP
0.84
MPC
2.6
ClinPred
0.99
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.70
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747956857; hg19: chr9-26946976; API