rs1233022871

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-43923962-C-A
• chr22-43923962-C-G
• chr22-43923962-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Synonymous variant affecting the same amino acid position (i.e. F17F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNPLA3 NM_025225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 1 publications found

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]

ENSG00000304926 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025225.3. 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
	PNPLA3	NM_025225.3	MANE Select	c.51C>A	p.Phe17Leu	missense	Exon 1 of 9	NP_079501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.51C>A	p.Phe17Leu	missense	Exon 1 of 9	ENSP00000216180.3	Q9NST1-1
	PNPLA3	ENST00000862822.1		c.51C>A	p.Phe17Leu	missense	Exon 1 of 9	ENSP00000532881.1
	PNPLA3	ENST00000862819.1		c.51C>A	p.Phe17Leu	missense	Exon 1 of 9	ENSP00000532878.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 212466 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.89
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.73		Loss of helix (P = 0.079)
MVP		0.89
MPC		0.28
ClinPred		0.98	D
GERP RS		1.4
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.59
gMVP		0.60
Mutation Taster		=58/42	polymorphism

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