Variant 22-43928850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025225.3(PNPLA3):c.447C>T(p.Pro149Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,606,722 control chromosomes in the GnomAD database, including 47,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4553 hom., cov: 30)

Exomes 𝑓: 0.23 ( 43301 hom. )

Consequence

PNPLA3
NM_025225.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.31

Variant links:

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 links:

PNPLA3 (HGNC:):

PNPLA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-43928850-C-T is Benign according to our data. Variant chr22-43928850-C-T is described in ClinVar as [Benign]. Clinvar id is 341933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA3	NM_025225.3 linkuse as main transcript	c.447C>T	p.Pro149Pro	synonymous_variant	3/9	ENST00000216180.8	NP_079501.2	Q9NST1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8 linkuse as main transcript	c.447C>T	p.Pro149Pro	synonymous_variant	3/9	1	NM_025225.3	ENSP00000216180.3		Q9NST1-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34587

AN:

151580

Hom.:

4551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.278

AC:

69774

AN:

251164

Hom.:

11853

AF XY:

0.267

AC XY:

36269

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.550

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.381

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.233

AC:

338558

AN:

1455024

Hom.:

43301

Cov.:

AF XY:

0.232

AC XY:

167976

AN XY:

724274

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.228

AC:

34593

AN:

151698

Hom.:

4553

Cov.:

AF XY:

0.233

AC XY:

17300

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.219

Hom.:

1992

Bravo

AF:

0.245

Asia WGS

AF:

0.296

AC:

1026

AN:

3478

EpiCase

AF:

0.238

EpiControl

AF:

0.242

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 07, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 25, 2019

The p.Pro149Pro variant in PNPLA3 is classified as benign because it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. It has been identified in 55% (19436/35384, including 5584 homozygous observations) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1, BP4, BP7. -

NAFLD1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.28

DANN

Benign

0.42

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over