chr22-43933198-C-T

Position:

• chr22-43933198-C-T

Variant summary

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

The NM_025225.3(PNPLA3):​c.696+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,024,752 control chromosomes in the GnomAD database, including 22,126 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 0.18 (3162 hom., cov: 31)
  • Exomes 𝑓: 0.19 (18964 hom.)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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]

PNPLA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.696+111C>T		intron_variant		ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.696+111C>T		intron_variant		1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.684+111C>T		intron_variant		2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.*328+111C>T		intron_variant		2		ENSP00000384668.2
PNPLA3	ENST00000497129.1	n.81+111C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28035 AN: 151780 Hom.: 3160 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.189 AC: 165282 AN: 872854 Hom.: 18964 AF XY: 0.189 AC XY: 84696 AN XY: 448372

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.185 AC: 28041 AN: 151898 Hom.: 3162 Cov.: 31 AF XY: 0.191 AC XY: 14207 AN XY: 74206

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.193

Alfa AF: 0.179 Hom.: 1451

Bravo AF: 0.200

Asia WGS AF: 0.287 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.47

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: rs2076211; hg19: chr22-44329078; COSMIC: COSV53379317; COSMIC: COSV53379317;