6-46705189-T-C

Variant names:

• chr6-46705189-T-C
• rs371623990
• NM_005084.4:c.1153A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005084.4(PLA2G7):​c.1153A>G​(p.Asn385Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000224 in 1,609,094 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3306025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1153A>G	p.Asn385Asp	missense_variant	Exon 11 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1153A>G	p.Asn385Asp	missense_variant	Exon 11 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1153A>G	p.Asn385Asp	missense_variant	Exon 11 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	c.1018A>G	p.Asn340Asp	missense_variant	Exon 10 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.1153A>G	p.Asn385Asp	missense_variant	Exon 11 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1153A>G	p.Asn385Asp	missense_variant	Exon 11 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250772 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000892 AC: 13 AN: 1456864 Hom.: 0 Cov.: 28 AF XY: 0.00000690 AC XY: 5 AN XY: 725114

African (AFR) AF: 0.000150 AC: 5 AN: 33366

American (AMR) AF: 0.0000672 AC: 3 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5736

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107704

Other (OTH) AF: 0.0000498 AC: 3 AN: 60212

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74366

African (AFR) AF: 0.000506 AC: 21 AN: 41470

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000967 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1153A>G (p.N385D) alteration is located in exon 11 (coding exon 10) of the PLA2G7 gene. This alteration results from a A to G substitution at nucleotide position 1153, causing the asparagine (N) at amino acid position 385 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		4.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.29
Sift	Benign	0.097	T;T
Sift4G	Benign	0.088	T;T
Polyphen		0.99	D;D
Vest4		0.33
MVP		0.57
MPC		0.010
ClinPred		0.24	T
GERP RS		4.7
Varity_R		0.90
gMVP		0.87
Mutation Taster		=51/49	polymorphism

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: rs371623990; hg19: chr6-46672926;