Genetic Variant NM_001098537.3:c.2798C>G (chr9-137478118-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001098537.3(PNPLA7):c.2798C>G(p.Pro933Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,347,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098537.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA7	NM_001098537.3	MANE Select	c.2798C>G	p.Pro933Arg	missense	Exon 25 of 35	NP_001092007.2
	PNPLA7	NM_152286.5		c.2723C>G	p.Pro908Arg	missense	Exon 24 of 34	NP_689499.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PNPLA7	ENST00000406427.6	TSL:1 MANE Select	c.2798C>G	p.Pro933Arg	missense	Exon 25 of 35	ENSP00000384610.1
PNPLA7	ENST00000277531.8	TSL:2	c.2723C>G	p.Pro908Arg	missense	Exon 24 of 34	ENSP00000277531.4
PNPLA7	ENST00000469998.1	TSL:2	n.1537C>G		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

34230

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000167

AC:

AN:

1195352

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

576494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23850

American (AMR)

AF:

0.00

AC:

AN:

10608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16662

East Asian (EAS)

AF:

0.00

AC:

AN:

27310

South Asian (SAS)

AF:

0.000407

AC:

AN:

46660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.00000103

AC:

AN:

974324

Other (OTH)

AF:

0.00

AC:

AN:

48154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000190

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.1

PhyloP100

9.3

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.30

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

0.98

Vest4

0.48

MutPred

0.29

Gain of MoRF binding (P = 0.0025)

MVP

0.25

MPC

0.72

ClinPred

0.99

GERP RS

4.7

Varity_R

0.19

gMVP

0.49

Mutation Taster

=57/43

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over