NM_017839.5:c.553G>C

Variant names:

• chr16-55529858-G-C
• rs777807704
• NM_017839.5:c.553G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_017839.5(LPCAT2):​c.553G>C​(p.Val185Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,234 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (1 hom.)
• Consequence: LPCAT2 NM_017839.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92
• Publications: 0 publications found

Genes affected

LPCAT2 (HGNC:26032): (lysophosphatidylcholine acyltransferase 2) This gene encodes a member of the lysophospholipid acyltransferase family. The encoded enzyme may function in two ways: to catalyze the biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) from 1-O-alkyl-sn-glycero-3-phosphocholine, and to catalyze the synthesis of glycerophospholipid precursors from arachidonyl-CoA and lysophosphatidylcholine. The encoded protein may function in membrane biogenesis and production of platelet-activating factor in inflammatory cells. The enzyme may localize to the endoplasmic reticulum and the Golgi. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017839.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT2	NM_017839.5	MANE Select	c.553G>C	p.Val185Leu	missense	Exon 4 of 14	NP_060309.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT2	ENST00000262134.10	TSL:1 MANE Select	c.553G>C	p.Val185Leu	missense	Exon 4 of 14	ENSP00000262134.5	Q7L5N7-1
	LPCAT2	ENST00000947554.1		c.553G>C	p.Val185Leu	missense	Exon 4 of 14	ENSP00000617613.1
	LPCAT2	ENST00000929287.1		c.553G>C	p.Val185Leu	missense	Exon 4 of 13	ENSP00000599346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459234 Hom.: 1 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725756

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53098

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110994

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.7	L
PhyloP100		3.9
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.57
Sift	Benign	0.040	D
Sift4G	Uncertain	0.058	T
Polyphen		0.73	P
Vest4		0.70
MutPred		0.61		Loss of MoRF binding (P = 0.1136)
MVP		0.75
MPC		0.82
ClinPred		0.74	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777807704; hg19: chr16-55563770;