rs10511793

Variant names:

• chr9-26924623-T-C
• rs10511793
• NM_001031689.3:c.869+1202A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397292.8(PLAA):​c.869+1202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,120 control chromosomes in the GnomAD database, including 4,020 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4020 hom., cov: 32)
• Consequence: PLAA ENST00000397292.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 3 publications found

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]

PLAA Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397292.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAA	NM_001031689.3	MANE Select	c.869+1202A>G		intron	N/A	NP_001026859.1
	PLAA	NM_001321546.2		c.869+1202A>G		intron	N/A	NP_001308475.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAA	ENST00000397292.8	TSL:1 MANE Select	c.869+1202A>G		intron	N/A	ENSP00000380460.3
	PLAA	ENST00000520884.5	TSL:2	c.869+1202A>G		intron	N/A	ENSP00000429372.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31803 AN: 152002 Hom.: 4004 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31862 AN: 152120 Hom.: 4020 Cov.: 32 AF XY: 0.207 AC XY: 15381 AN XY: 74368

African (AFR) AF: 0.347 AC: 14383 AN: 41474

American (AMR) AF: 0.153 AC: 2332 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3466

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5176

South Asian (SAS) AF: 0.241 AC: 1160 AN: 4820

European-Finnish (FIN) AF: 0.121 AC: 1286 AN: 10594

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10981 AN: 67992

Other (OTH) AF: 0.223 AC: 471 AN: 2112

Alfa AF: 0.180 Hom.: 1422

Bravo AF: 0.214

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.7
DANN	Benign	0.82
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10511793; hg19: chr9-26924621;