chr15-42079554-A-T

Position:

• chr15-42079554-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178034.4(PLA2G4D):​c.1300T>A​(p.Ser434Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,603,226 control chromosomes in the GnomAD database, including 101,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.32 (8691 hom., cov: 34)
  • Exomes 𝑓: 0.35 (92800 hom.)
• Consequence: PLA2G4D NM_178034.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.926588E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4D	NM_178034.4	c.1300T>A	p.Ser434Thr	missense_variant	13/20	ENST00000290472.4	NP_828848.3
PLA2G4D	XM_047432399.1	c.1300T>A	p.Ser434Thr	missense_variant	13/20		XP_047288355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4D	ENST00000290472.4	c.1300T>A	p.Ser434Thr	missense_variant	13/20	1	NM_178034.4	ENSP00000290472.3

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49213 AN: 151972 Hom.: 8678 Cov.: 34

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.363 AC: 85417 AN: 235162 Hom.: 16654 AF XY: 0.352 AC XY: 45086 AN XY: 128256

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.239

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.352 AC: 510623 AN: 1451136 Hom.: 92800 Cov.: 45 AF XY: 0.348 AC XY: 251097 AN XY: 722100

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.324 AC: 49245 AN: 152090 Hom.: 8691 Cov.: 34 AF XY: 0.325 AC XY: 24176 AN XY: 74352

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.317

Alfa AF: 0.349 Hom.: 6381

Bravo AF: 0.324

TwinsUK AF: 0.359 AC: 1333

ALSPAC AF: 0.339 AC: 1305

ESP6500AA AF: 0.196 AC: 864

ESP6500EA AF: 0.347 AC: 2980

ExAC AF: 0.350 AC: 42391

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.00029	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.47	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.024
Sift	Benign	0.30	T
Sift4G	Benign	0.38	T
Polyphen		0.17	B
Vest4		0.092
MPC		0.055
ClinPred		0.0034	T
GERP RS		1.3
Varity_R		0.27
gMVP		0.29

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: rs4924618; hg19: chr15-42371752; COSMIC: COSV51819406; COSMIC: COSV51819406;