Genetic Variant PNPLA7:p.Pro933Leu (chr9-137478118-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001098537.3(PNPLA7):c.2798C>T(p.Pro933Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,347,618 control chromosomes in the GnomAD database, including 370 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 0.0053 ( 51 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 319 hom. )

Consequence

PNPLA7
NM_001098537.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.26

Publications

10 publications found

Variant links:

Genes affected

PNPLA7 (HGNC:24768): (patatin like phospholipase domain containing 7) Human patatin-like phospholipases, such as PNPLA7, have been implicated in regulation of adipocyte differentiation and have been induced by metabolic stimuli (Wilson et al., 2006 [PubMed 16799181]).[supplied by OMIM, Jun 2008]

PNPLA7 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 (MetaRNN=0.0019916296).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNPLA7	NM_001098537.3 link	c.2798C>T	p.Pro933Leu	missense_variant	Exon 25 of 35	ENST00000406427.6	NP_001092007.2	Q6ZV29-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PNPLA7	ENST00000406427.6 link	c.2798C>T	p.Pro933Leu	missense_variant	Exon 25 of 35	1	NM_001098537.3	ENSP00000384610.1	Q6ZV29-5
PNPLA7	ENST00000277531.8 link	c.2723C>T	p.Pro908Leu	missense_variant	Exon 24 of 34	2		ENSP00000277531.4	Q6ZV29-1
PNPLA7	ENST00000469998.1 link	n.1537C>T		non_coding_transcript_exon_variant	Exon 2 of 10	2
PNPLA7	ENST00000492278.5 link	n.1314C>T		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.00533

AC:

811

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00739

AC:

253

AN:

34230

AF XY:

0.00742

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.000518

Gnomad OTH exome

AF:

0.00871

GnomAD4 exome

AF:

0.00423

AC:

5051

AN:

1195346

Hom.:

319

Cov.:

AF XY:

0.00409

AC XY:

2357

AN XY:

576490

show subpopulations

African (AFR)

AF:

0.000797

AC:

AN:

23850

American (AMR)

AF:

0.000283

AC:

AN:

10608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16662

East Asian (EAS)

AF:

0.144

AC:

3942

AN:

27306

South Asian (SAS)

AF:

0.00259

AC:

121

AN:

46660

European-Finnish (FIN)

AF:

0.00186

AC:

AN:

42896

Middle Eastern (MID)

AF:

0.00143

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.000520

AC:

507

AN:

974322

Other (OTH)

AF:

0.00773

AC:

372

AN:

48154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

248

496

745

993

1241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.00532

AC:

810

AN:

152272

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

465

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41566

American (AMR)

AF:

0.000719

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.120

AC:

621

AN:

5174

South Asian (SAS)

AF:

0.00767

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

67988

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00438

Hom.:

Bravo

AF:

0.00564

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.000354

AC:

ExAC

AF:

0.00598

AC:

631

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;.

PhyloP100

9.3

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.89

P;D

Vest4

0.46

MVP

0.19

MPC

0.62

ClinPred

0.099

GERP RS

4.7

Varity_R

0.22

gMVP

0.52

Mutation Taster

=81/19

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over