22-43942254-T-C

Variant names:

• chr22-43942254-T-C
• rs3810622
• NM_025225.3:c.1112+2129T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025225.3(PNPLA3):​c.1112+2129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,030 control chromosomes in the GnomAD database, including 12,428 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12428 hom., cov: 32)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

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.1112+2129T>C		intron	N/A	NP_079501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.1112+2129T>C		intron	N/A	ENSP00000216180.3	Q9NST1-1
	PNPLA3	ENST00000862822.1		c.1142+2129T>C		intron	N/A	ENSP00000532881.1
	PNPLA3	ENST00000862819.1		c.1136+2129T>C		intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60903 AN: 151914 Hom.: 12405 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60963 AN: 152030 Hom.: 12428 Cov.: 32 AF XY: 0.399 AC XY: 29645 AN XY: 74308

African (AFR) AF: 0.374 AC: 15499 AN: 41462

American (AMR) AF: 0.320 AC: 4891 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2214 AN: 5174

South Asian (SAS) AF: 0.515 AC: 2472 AN: 4800

European-Finnish (FIN) AF: 0.413 AC: 4363 AN: 10552

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28780 AN: 67974

Other (OTH) AF: 0.393 AC: 830 AN: 2114

Alfa AF: 0.413 Hom.: 22204

Bravo AF: 0.390

Asia WGS AF: 0.477 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3810622; hg19: chr22-44338134;