NM_001031689.3:c.150-5519G>A

Variant names:

• chr9-26940725-C-T
• rs12003612
• NM_001031689.3:c.150-5519G>A

Variant summary

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

The NM_001031689.3(PLAA):​c.150-5519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,088 control chromosomes in the GnomAD database, including 1,108 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 0.11 (1108 hom., cov: 32)
• Consequence: PLAA NM_001031689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAA	NM_001031689.3	c.150-5519G>A		intron_variant	Intron 1 of 13	ENST00000397292.8	NP_001026859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAA	ENST00000397292.8	c.150-5519G>A		intron_variant	Intron 1 of 13	1	NM_001031689.3	ENSP00000380460.3
PLAA	ENST00000520884.5	c.150-5519G>A		intron_variant	Intron 1 of 12	2		ENSP00000429372.1
PLAA	ENST00000523212.1	c.87-5528G>A		intron_variant	Intron 1 of 5	3		ENSP00000428111.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17378 AN: 151970 Hom.: 1104 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.114 AC: 17410 AN: 152088 Hom.: 1108 Cov.: 32 AF XY: 0.112 AC XY: 8347 AN XY: 74314

African (AFR) AF: 0.176 AC: 7301 AN: 41476

American (AMR) AF: 0.0886 AC: 1355 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3472

East Asian (EAS) AF: 0.0267 AC: 138 AN: 5174

South Asian (SAS) AF: 0.116 AC: 557 AN: 4820

European-Finnish (FIN) AF: 0.0760 AC: 803 AN: 10564

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0940 AC: 6392 AN: 67970

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.101 Hom.: 1259

Bravo AF: 0.116

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.65
PhyloP100		-0.42
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: rs12003612; hg19: chr9-26940723;