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GeneBe

9-26905604-A-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_001031689.3(PLAA):c.2295T>G(p.Ser765=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,613,942 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

PLAA
NM_001031689.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.140
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-26905604-A-C is Benign according to our data. Variant chr9-26905604-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1588427.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.14 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000289 (44/152212) while in subpopulation AMR AF= 0.000589 (9/15284). AF 95% confidence interval is 0.000307. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLAANM_001031689.3 linkuse as main transcriptc.2295T>G p.Ser765= synonymous_variant 14/14 ENST00000397292.8
PLAANM_001321546.2 linkuse as main transcriptc.2226T>G p.Ser742= synonymous_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLAAENST00000397292.8 linkuse as main transcriptc.2295T>G p.Ser765= synonymous_variant 14/141 NM_001031689.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000289
AC:
44
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000283
AC:
71
AN:
251254
Hom.:
0
AF XY:
0.000280
AC XY:
38
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.000595
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.000361
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000263
AC:
385
AN:
1461730
Hom.:
0
Cov.:
31
AF XY:
0.000243
AC XY:
177
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.000650
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.000278
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000289
AC:
44
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.000309
AC XY:
23
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00143
Alfa
AF:
0.000376
Hom.:
0
Bravo
AF:
0.000310
EpiCase
AF:
0.000491
EpiControl
AF:
0.000474

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
7.6
Dann
Benign
0.71

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: rs142598453; hg19: chr9-26905602; API