22-43928075-T-C

Variant names:

• chr22-43928075-T-C
• rs738407
• NM_025225.3:c.421-749T>C

Variant summary

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

The ENST00000216180.8(PNPLA3):​c.421-749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,134 control chromosomes in the GnomAD database, including 12,844 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 0.41 (12844 hom., cov: 33)
• Consequence: PNPLA3 ENST00000216180.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000216180.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	NM_025225.3	MANE Select	c.421-749T>C		intron	N/A	NP_079501.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.421-749T>C		intron	N/A	ENSP00000216180.3
	PNPLA3	ENST00000423180.2	TSL:2	c.409-749T>C		intron	N/A	ENSP00000397987.2
	PNPLA3	ENST00000406117.6	TSL:2	n.*53-749T>C		intron	N/A	ENSP00000384668.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61646 AN: 152016 Hom.: 12835 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.405 AC: 61680 AN: 152134 Hom.: 12844 Cov.: 33 AF XY: 0.414 AC XY: 30764 AN XY: 74360

African (AFR) AF: 0.382 AC: 15851 AN: 41506

American (AMR) AF: 0.508 AC: 7766 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2929 AN: 5174

South Asian (SAS) AF: 0.463 AC: 2234 AN: 4820

European-Finnish (FIN) AF: 0.465 AC: 4912 AN: 10568

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25576 AN: 67988

Other (OTH) AF: 0.375 AC: 793 AN: 2114

Alfa AF: 0.380 Hom.: 18507

Bravo AF: 0.408

Asia WGS AF: 0.493 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.78
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: rs738407; hg19: chr22-44323955;