rs747331639

Positions:

• chr22-38145508-T-C
• chr22-38145508-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003560.4(PLA2G6):​c.355A>G​(p.Ser119Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLA2G6 NM_003560.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

Genes affected

PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31113076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.355A>G	p.Ser119Gly	missense_variant	3/17	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.355A>G	p.Ser119Gly	missense_variant	3/17	1	NM_003560.4	ENSP00000333142	P3
	ENST00000624072.1	n.15293T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460940 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726668

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;.;.;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T;T;.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.2	L;L;L;.
MutationTaster	Benign	0.97	D;D;D;D;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.019	D;D;D;T
Sift4G	Benign	0.072	T;T;T;T
Polyphen		0.67	P;D;D;.
Vest4		0.097
MutPred		0.61		Gain of catalytic residue at S119 (P = 0.0048);Gain of catalytic residue at S119 (P = 0.0048);Gain of catalytic residue at S119 (P = 0.0048);Gain of catalytic residue at S119 (P = 0.0048);
MVP		0.90
MPC		0.22
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.16

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: rs747331639; hg19: chr22-38541515;