chr9-26945978-A-G

Variant names:

• chr9-26945978-A-G
• rs7035755
• NM_001031689.3:c.149+919T>C

Variant summary

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

The NM_001031689.3(PLAA):​c.149+919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,234 control chromosomes in the GnomAD database, including 1,090 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 (1090 hom., cov: 32)
• Consequence: PLAA NM_001031689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031689.3. 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.149+919T>C		intron	N/A	NP_001026859.1
	PLAA	NM_001321546.2		c.149+919T>C		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.149+919T>C		intron	N/A	ENSP00000380460.3
	PLAA	ENST00000520884.5	TSL:2	c.149+919T>C		intron	N/A	ENSP00000429372.1
	PLAA	ENST00000523212.1	TSL:3	c.86+919T>C		intron	N/A	ENSP00000428111.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17037 AN: 152116 Hom.: 1090 Cov.: 32

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.112 AC: 17053 AN: 152234 Hom.: 1090 Cov.: 32 AF XY: 0.113 AC XY: 8407 AN XY: 74412

African (AFR) AF: 0.0913 AC: 3794 AN: 41548

American (AMR) AF: 0.0777 AC: 1188 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3472

East Asian (EAS) AF: 0.113 AC: 587 AN: 5182

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4824

European-Finnish (FIN) AF: 0.0827 AC: 876 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8323 AN: 68008

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.124 Hom.: 1336

Bravo AF: 0.108

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.71
PhyloP100		-0.31
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: rs7035755; hg19: chr9-26945976;