NM_178034.4:c.2353A>T

Variant names:

• chr15-42068819-T-A
• rs1199935841
• NM_178034.4:c.2353A>T

Variant summary

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

The NM_178034.4(PLA2G4D):​c.2353A>T​(p.Ser785Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 33)
  • Exomes 𝑓: 0.0000027 (1 hom.)
• Consequence: PLA2G4D NM_178034.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.593

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=0.16285482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4D	NM_178034.4	c.2353A>T	p.Ser785Cys	missense_variant	Exon 20 of 20	ENST00000290472.4	NP_828848.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4D	ENST00000290472.4	c.2353A>T	p.Ser785Cys	missense_variant	Exon 20 of 20	1	NM_178034.4	ENSP00000290472.3
PLA2G4D	ENST00000560932.1	n.1506A>T		non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249672 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461570 Hom.: 1 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727076

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.57
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.086
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.072
MutPred		0.52		Loss of phosphorylation at S785 (P = 0.0808);
MVP		0.44
MPC		0.068
ClinPred		0.22	T
GERP RS		2.2
Varity_R		0.23
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1199935841; hg19: chr15-42361017;