Variant 22-43889339-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138814.4(PNPLA5):c.692C>T(p.Pro231Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

PNPLA5
NM_138814.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30719846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA5	NM_138814.4 linkuse as main transcript	c.692C>T	p.Pro231Leu	missense_variant	4/9	ENST00000216177.9	NP_620169.1	Q7Z6Z6-1
PNPLA5	NM_001177675.2 linkuse as main transcript	c.350C>T	p.Pro117Leu	missense_variant	2/7		NP_001171146.1	Q7Z6Z6-2
PNPLA5	NM_001371410.1 linkuse as main transcript	c.272C>T	p.Pro91Leu	missense_variant	4/9		NP_001358339.1
PNPLA5	XM_047441164.1 linkuse as main transcript	c.272C>T	p.Pro91Leu	missense_variant	2/7		XP_047297120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PNPLA5	ENST00000216177.9 linkuse as main transcript	c.692C>T	p.Pro231Leu	missense_variant	4/9	1	NM_138814.4	ENSP00000216177.3	Q7Z6Z6-1
PNPLA5	ENST00000381198.7 linkuse as main transcript	c.350C>T	p.Pro117Leu	missense_variant	2/7	2		ENSP00000370595.2	Q7Z6Z6-2
PNPLA5	ENST00000438734.1 linkuse as main transcript	c.427-1688C>T		intron_variant		3		ENSP00000405732.1	B1AHL9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250848

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000978

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000330

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

Feb 15, 2023

The c.692C>T (p.P231L) alteration is located in exon 4 (coding exon 4) of the PNPLA5 gene. This alteration results from a C to T substitution at nucleotide position 692, causing the proline (P) at amino acid position 231 to be replaced by a leucine (L). 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

0.17

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

T;T;.;.

Eigen

Benign

0.087

Eigen_PC

Benign

0.021

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.49

.;T;T;.

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.3

M;M;.;.

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-8.9

.;D;.;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

.;D;.;D

Sift4G

Uncertain

0.040

D;D;T;T

Polyphen

0.78

P;P;B;B

Vest4

0.23

MVP

0.76

MPC

0.14

ClinPred

0.83

GERP RS

4.9

Varity_R

0.55

gMVP

0.82

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

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