NM_012320.4:c.-51A>T

Variant names:

• chr16-68245376-A-T
• rs9935022
• NM_012320.4:c.-51A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012320.4(PLA2G15):​c.-51A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 1,582,552 control chromosomes in the GnomAD database, including 753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (378 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (375 hom.)
• Consequence: PLA2G15 NM_012320.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 1 publications found

Genes affected

PLA2G15 (HGNC:17163): (phospholipase A2 group XV) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene hydrolyzes lysophosphatidylcholine to glycerophosphorylcholine and a free fatty acid. This enzyme is present in the plasma and thought to be associated with high-density lipoprotein. A later paper contradicts the function of this gene. It demonstrates that this gene encodes a lysosomal enzyme instead of a lysophospholipase and has both calcium-independent phospholipase A2 and transacylase activities. [provided by RefSeq, Jul 2008]

ENSG00000307195 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012320.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G15	NM_012320.4	MANE Select	c.-51A>T		5_prime_UTR	Exon 1 of 6	NP_036452.1
	PLA2G15	NM_001363551.2		c.-51A>T		5_prime_UTR	Exon 1 of 6	NP_001350480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G15	ENST00000219345.10	TSL:1 MANE Select	c.-51A>T		5_prime_UTR	Exon 1 of 6	ENSP00000219345.5
	PLA2G15	ENST00000566978.1	TSL:2	n.-51A>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000457049.1
	PLA2G15	ENST00000413021.2	TSL:2	c.-51A>T		5_prime_UTR	Exon 1 of 5	ENSP00000394197.2

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6105 AN: 152110 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0307

GnomAD2 exomes AF: 0.0117 AC: 2674 AN: 228658 AF XY: 0.00908

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.00893

Gnomad ASJ exome AF: 0.00873

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00252

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.00667

GnomAD4 exome AF: 0.00605 AC: 8659 AN: 1430324 Hom.: 375 Cov.: 31 AF XY: 0.00550 AC XY: 3905 AN XY: 710020

African (AFR) AF: 0.144 AC: 4736 AN: 32776

American (AMR) AF: 0.0100 AC: 431 AN: 43062

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 269 AN: 25394

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39036

South Asian (SAS) AF: 0.000469 AC: 40 AN: 85364

European-Finnish (FIN) AF: 0.00252 AC: 99 AN: 39284

Middle Eastern (MID) AF: 0.0234 AC: 133 AN: 5688

European-Non Finnish (NFE) AF: 0.00201 AC: 2209 AN: 1100402

Other (OTH) AF: 0.0125 AC: 741 AN: 59318

GnomAD4 genome AF: 0.0402 AC: 6124 AN: 152228 Hom.: 378 Cov.: 32 AF XY: 0.0387 AC XY: 2883 AN XY: 74442

African (AFR) AF: 0.134 AC: 5557 AN: 41514

American (AMR) AF: 0.0183 AC: 280 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 68012

Other (OTH) AF: 0.0299 AC: 63 AN: 2108

Alfa AF: 0.0236 Hom.: 25

Bravo AF: 0.0449

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.6
DANN	Benign	0.63
PhyloP100		-0.23
PromoterAI		-0.025	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9935022; hg19: chr16-68279279;