Variant 9-137462185-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001098537.3(PNPLA7):c.3639G>T(p.Glu1213Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PNPLA7
NM_001098537.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.705

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA7	NM_001098537.3 link	c.3639G>T	p.Glu1213Asp	missense_variant	31/35	ENST00000406427.6	NP_001092007.2	Q6ZV29-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PNPLA7	ENST00000406427.6 link	c.3639G>T	p.Glu1213Asp	missense_variant	31/35	1	NM_001098537.3	ENSP00000384610.1	Q6ZV29-5
PNPLA7	ENST00000277531.8 link	c.3564G>T	p.Glu1188Asp	missense_variant	30/34	2		ENSP00000277531.4	Q6ZV29-1
PNPLA7	ENST00000469998.1 link	n.2522G>T		non_coding_transcript_exon_variant	7/10	2
PNPLA7	ENST00000492278.5 link	n.3233G>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412448

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696368

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2023

The c.3639G>T (p.E1213D) alteration is located in exon 31 (coding exon 31) of the PNPLA7 gene. This alteration results from a G to T substitution at nucleotide position 3639, causing the glutamic acid (E) at amino acid position 1213 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Uncertain

0.32

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.7

D;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.077

T;T

Polyphen

0.99

D;D

Vest4

0.82

MutPred

0.46

Loss of methylation at K1185 (P = 0.1026);.;

MVP

0.39

MPC

0.68

ClinPred

0.94

GERP RS

3.4

Varity_R

0.29

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over