Genetic Variant NM_025225.3:c.1112+93T>C (chr22-43940218-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.555

Publications

20 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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+93T>C		intron	N/A	NP_079501.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.1112+93T>C	intron	N/A	ENSP00000216180.3	Q9NST1-1
PNPLA3	ENST00000862822.1		c.1142+93T>C	intron	N/A	ENSP00000532881.1
PNPLA3	ENST00000862819.1		c.1136+93T>C	intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30931

AN:

152026

Hom.:

3669

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.165

AC:

4713

AN:

28538

American (AMR)

AF:

0.488

AC:

17478

AN:

35828

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

3849

AN:

23614

East Asian (EAS)

AF:

0.421

AC:

15048

AN:

35702

South Asian (SAS)

AF:

0.211

AC:

16025

AN:

75810

European-Finnish (FIN)

AF:

0.231

AC:

11160

AN:

48316

Middle Eastern (MID)

AF:

0.195

AC:

980

AN:

5016

European-Non Finnish (NFE)

AF:

0.167

AC:

158873

AN:

951248

Other (OTH)

AF:

0.189

AC:

10034

AN:

53182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9169

18337

27506

36674

45843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5578

11156

16734

22312

27890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.203

AC:

30938

AN:

152146

Hom.:

3669

Cov.:

AF XY:

0.211

AC XY:

15711

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.166

AC:

6881

AN:

41512

American (AMR)

AF:

0.374

AC:

5721

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

553

AN:

3468

East Asian (EAS)

AF:

0.395

AC:

2040

AN:

5166

South Asian (SAS)

AF:

0.224

AC:

1082

AN:

4826

European-Finnish (FIN)

AF:

0.231

AC:

2441

AN:

10590

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11566

AN:

67988

Other (OTH)

AF:

0.206

AC:

435

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1202

2404

3606

4808

6010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.181

Hom.:

2330

Bravo

AF:

0.217

Asia WGS

AF:

0.291

AC:

1010

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.89

(source)

DANN

Benign

0.58

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over