chr22-38145508-T-G

Position:

• chr22-38145508-T-G

Variant summary

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

The ENST00000332509.8(PLA2G6):​c.355A>C​(p.Ser119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLA2G6 ENST00000332509.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.355A>C	p.Ser119Arg	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>C	p.Ser119Arg	missense_variant	3/17	1	NM_003560.4	ENSP00000333142	P3
	ENST00000624072.1	n.15293T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Infantile neuroaxonal dystrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

May 03, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D;.;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.4	L;L;L;.
MutationTaster	Benign	0.99	D;D;D;D;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Benign	0.083	T;T;T;D
Polyphen		0.94	P;D;D;.
Vest4		0.52
MutPred		0.68		Gain of MoRF binding (P = 0.0852);Gain of MoRF binding (P = 0.0852);Gain of MoRF binding (P = 0.0852);Gain of MoRF binding (P = 0.0852);
MVP		0.90
MPC		0.44
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.54
gMVP		0.34

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;