NM_025225.3:c.51C>A

Variant names:

• chr22-43923962-C-A
• rs1233022871
• NM_025225.3:c.51C>A

Variant summary

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

The NM_025225.3(PNPLA3):​c.51C>A​(p.Phe17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNPLA3 NM_025225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888

Genes affected

PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 9	ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 9	1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 9	2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.51C>A		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000384668.2
PNPLA3	ENST00000478713.1	n.-152C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.44
MutPred		0.73		Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.89
MPC		0.28
ClinPred		0.98	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.59
gMVP		0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1233022871; hg19: chr22-44319842; COSMIC: COSV53378073; COSMIC: COSV53378073;