NM_005084.4:c.1142T>C

Variant names:

• chr6-46705200-A-G
• rs1351406965
• NM_005084.4:c.1142T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005084.4(PLA2G7):​c.1142T>C​(p.Ile381Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,608,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• Publications: 0 publications found

Genes affected

PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005084.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	NM_005084.4	MANE Select	c.1142T>C	p.Ile381Thr	missense	Exon 11 of 12	NP_005075.3
	PLA2G7	NM_001168357.2		c.1142T>C	p.Ile381Thr	missense	Exon 11 of 12	NP_001161829.1	Q13093

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	ENST00000274793.12	TSL:1 MANE Select	c.1142T>C	p.Ile381Thr	missense	Exon 11 of 12	ENSP00000274793.7	Q13093
	PLA2G7	ENST00000537365.1	TSL:1	c.1142T>C	p.Ile381Thr	missense	Exon 11 of 12	ENSP00000445666.1	Q13093
	PLA2G7	ENST00000878321.1		c.1142T>C	p.Ile381Thr	missense	Exon 11 of 12	ENSP00000548380.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456200 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724834

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000300 AC: 1 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107136

Other (OTH) AF: 0.00 AC: 0 AN: 60170

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.0000724 AC: 3 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		8.9
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.26
Sift	Benign	0.046	D
Sift4G	Benign	0.45	T
Polyphen		0.31	B
Vest4		0.48
MutPred		0.68		Loss of stability (P = 3e-04)
MVP		0.53
MPC		0.019
ClinPred		0.84	D
GERP RS		5.9
Varity_R		0.51
gMVP		0.64
Mutation Taster		=48/52	disease causing

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: rs1351406965; hg19: chr6-46672937;