22-43940218-T-C

Variant names:

• chr22-43940218-T-C
• rs1010023
• NM_025225.3:c.1112+93T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025225.3(PNPLA3):​c.1112+93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,409,400 control chromosomes in the GnomAD database, including 29,535 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 0.20 (3669 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25866 hom.)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.1112+93T>C		intron_variant	Intron 7 of 8	ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.1112+93T>C		intron_variant	Intron 7 of 8	1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.1100+93T>C		intron_variant	Intron 7 of 8	2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.*744+93T>C		intron_variant	Intron 7 of 9	2		ENSP00000384668.2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30931 AN: 152026 Hom.: 3669 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.189 AC: 238160 AN: 1257254 Hom.: 25866 AF XY: 0.189 AC XY: 118326 AN XY: 625320

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.203 AC: 30938 AN: 152146 Hom.: 3669 Cov.: 32 AF XY: 0.211 AC XY: 15711 AN XY: 74396

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.206

Alfa AF: 0.180 Hom.: 1497

Bravo AF: 0.217

Asia WGS AF: 0.291 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1010023; hg19: chr22-44336098; COSMIC: COSV53378114; COSMIC: COSV53378114;