Genetic Variant NM_025225.3:c.979+20A>G (chr22-43937292-A-G) – 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.979+20A>G 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 1,602,366 control chromosomes in the GnomAD database, including 33,624 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 ( 3664 hom., cov: 33)

Exomes 𝑓: 0.19 ( 29960 hom. )

Consequence

PNPLA3
NM_025225.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

15 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 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.979+20A>G		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.979+20A>G	intron	N/A	ENSP00000216180.3	Q9NST1-1
PNPLA3	ENST00000862822.1		c.1009+20A>G	intron	N/A	ENSP00000532881.1
PNPLA3	ENST00000862819.1		c.1003+20A>G	intron	N/A	ENSP00000532878.1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30910

AN:

152024

Hom.:

3664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.208

GnomAD2 exomes

AF:

0.247

AC:

60247

AN:

244280

AF XY:

0.234

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.512

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.189

AC:

274362

AN:

1450224

Hom.:

29960

Cov.:

AF XY:

0.189

AC XY:

136126

AN XY:

721514

show subpopulations

African (AFR)

AF:

0.166

AC:

5514

AN:

33290

American (AMR)

AF:

0.497

AC:

21994

AN:

44256

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

4233

AN:

26012

East Asian (EAS)

AF:

0.419

AC:

16568

AN:

39564

South Asian (SAS)

AF:

0.210

AC:

18004

AN:

85910

European-Finnish (FIN)

AF:

0.230

AC:

11775

AN:

51242

Middle Eastern (MID)

AF:

0.194

AC:

1079

AN:

5572

European-Non Finnish (NFE)

AF:

0.167

AC:

183936

AN:

1104374

Other (OTH)

AF:

0.188

AC:

11259

AN:

60004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12185

24370

36554

48739

60924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6722

13444

20166

26888

33610

<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:

30917

AN:

152142

Hom.:

3664

Cov.:

AF XY:

0.211

AC XY:

15698

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.166

AC:

6874

AN:

41528

American (AMR)

AF:

0.374

AC:

5718

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

553

AN:

3466

East Asian (EAS)

AF:

0.394

AC:

2030

AN:

5154

South Asian (SAS)

AF:

0.224

AC:

1077

AN:

4818

European-Finnish (FIN)

AF:

0.231

AC:

2445

AN:

10600

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11566

AN:

67984

Other (OTH)

AF:

0.206

AC:

435

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1239

2478

3716

4955

6194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.179

Hom.:

728

Bravo

AF:

0.217

Asia WGS

AF:

0.292

AC:

1011

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.028

(source)

DANN

Benign

0.23

PhyloP100

-1.5

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