Genetic Variant PNPLA5:c.*504A>C (chr22-43880291-T-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_138814.4(PNPLA5):c.*504A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 397,602 control chromosomes in the GnomAD database, including 151,886 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 0.88 ( 59865 hom., cov: 34)

Exomes 𝑓: 0.86 ( 92021 hom. )

Consequence

PNPLA5
NM_138814.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Publications

8 publications found

Variant links:

Genes affected

PNPLA5 (HGNC:24888): (patatin like phospholipase domain containing 5) This gene is a member of the patatin-like phospholipase family; its encoded protein has been shown to inhibit transacylation. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

PNPLA5 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PNPLA5	NM_138814.4 link	c.*504A>C	3_prime_UTR_variant	Exon 9 of 9	ENST00000216177.9	NP_620169.1	Q7Z6Z6-1
PNPLA5	NM_001177675.2 link	c.*504A>C	3_prime_UTR_variant	Exon 7 of 7		NP_001171146.1	Q7Z6Z6-2
PNPLA5	NM_001371410.1 link	c.*504A>C	3_prime_UTR_variant	Exon 9 of 9		NP_001358339.1
PNPLA5	XM_047441164.1 link	c.*504A>C	3_prime_UTR_variant	Exon 7 of 7		XP_047297120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA5	ENST00000216177.9 link	c.*504A>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_138814.4	ENSP00000216177.3		Q7Z6Z6-1
PNPLA5	ENST00000381198.7 link	c.*504A>C		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000370595.2		Q7Z6Z6-2

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134597

AN:

152150

Hom.:

59803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.943

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.877

Gnomad ASJ

AF:

0.773

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.946

Gnomad FIN

AF:

0.921

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.860

GnomAD4 exome

AF:

0.864

AC:

212006

AN:

245334

Hom.:

92021

Cov.:

AF XY:

0.862

AC XY:

107249

AN XY:

124396

show subpopulations

African (AFR)

AF:

0.945

AC:

6781

AN:

7176

American (AMR)

AF:

0.888

AC:

6595

AN:

7430

Ashkenazi Jewish (ASJ)

AF:

0.778

AC:

7178

AN:

9228

East Asian (EAS)

AF:

0.992

AC:

22674

AN:

22868

South Asian (SAS)

AF:

0.951

AC:

2204

AN:

2318

European-Finnish (FIN)

AF:

0.907

AC:

18831

AN:

20772

Middle Eastern (MID)

AF:

0.828

AC:

1072

AN:

1294

European-Non Finnish (NFE)

AF:

0.839

AC:

132553

AN:

157904

Other (OTH)

AF:

0.864

AC:

14118

AN:

16344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1443

2885

4328

5770

7213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.885

AC:

134720

AN:

152268

Hom.:

59865

Cov.:

AF XY:

0.889

AC XY:

66154

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.943

AC:

39187

AN:

41554

American (AMR)

AF:

0.877

AC:

13434

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.773

AC:

2685

AN:

3472

East Asian (EAS)

AF:

0.994

AC:

5135

AN:

5166

South Asian (SAS)

AF:

0.946

AC:

4565

AN:

4824

European-Finnish (FIN)

AF:

0.921

AC:

9773

AN:

10612

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

57027

AN:

68014

Other (OTH)

AF:

0.861

AC:

1818

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

797

1594

2390

3187

3984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.845

Hom.:

84218

Bravo

AF:

0.883

Asia WGS

AF:

0.966

AC:

3360

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.5

(source)

DANN

Benign

0.77

PhyloP100

-0.033

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over