chr15-42069972-C-G

Variant names:

• chr15-42069972-C-G
• rs750129637
• NM_178034.4:c.2167G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178034.4(PLA2G4D):​c.2167G>C​(p.Glu723Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,316,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PLA2G4D NM_178034.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

Genes affected

PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1747913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4D	NM_178034.4	c.2167G>C	p.Glu723Gln	missense_variant	Exon 19 of 20	ENST00000290472.4	NP_828848.3
PLA2G4D	XM_047432399.1	c.2167G>C	p.Glu723Gln	missense_variant	Exon 19 of 20		XP_047288355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4D	ENST00000290472.4	c.2167G>C	p.Glu723Gln	missense_variant	Exon 19 of 20	1	NM_178034.4	ENSP00000290472.3
PLA2G4D	ENST00000560932.1	n.1320G>C		non_coding_transcript_exon_variant	Exon 4 of 5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000159 AC: 21 AN: 1316854 Hom.: 0 Cov.: 31 AF XY: 0.0000108 AC XY: 7 AN XY: 645790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000201

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.020
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.051
Sift	Benign	0.13	T
Sift4G	Benign	0.32	T
Polyphen		0.97	D
Vest4		0.15
MutPred		0.33		Gain of disorder (P = 0.2373);
MVP		0.57
MPC		0.066
ClinPred		0.66	D
GERP RS		4.3
Varity_R		0.23
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs750129637; hg19: chr15-42362170;