Variant 22-43889378-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000216177.9(PNPLA5):c.653C>T(p.Thr218Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,614,042 control chromosomes in the GnomAD database, including 437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.027 ( 108 hom., cov: 32)

Exomes 𝑓: 0.019 ( 329 hom. )

Consequence

PNPLA5
ENST00000216177.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.486

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025170445).

BP6

Variant 22-43889378-G-A is Benign according to our data. Variant chr22-43889378-G-A is described in ClinVar as [Benign]. Clinvar id is 3038114.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PNPLA5	NM_138814.4 linkuse as main transcript	c.653C>T	p.Thr218Ile	missense_variant	4/9	ENST00000216177.9	NP_620169.1
PNPLA5	NM_001177675.2 linkuse as main transcript	c.311C>T	p.Thr104Ile	missense_variant	2/7		NP_001171146.1
PNPLA5	NM_001371410.1 linkuse as main transcript	c.233C>T	p.Thr78Ile	missense_variant	4/9		NP_001358339.1
PNPLA5	XM_047441164.1 linkuse as main transcript	c.233C>T	p.Thr78Ile	missense_variant	2/7		XP_047297120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA5	ENST00000216177.9 linkuse as main transcript	c.653C>T	p.Thr218Ile	missense_variant	4/9	1	NM_138814.4	ENSP00000216177	P1	Q7Z6Z6-1
PNPLA5	ENST00000381198.7 linkuse as main transcript	c.311C>T	p.Thr104Ile	missense_variant	2/7	2		ENSP00000370595		Q7Z6Z6-2
PNPLA5	ENST00000438734.1 linkuse as main transcript	c.426+1684C>T		intron_variant		3		ENSP00000405732

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4151

AN:

152112

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00997

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0221

GnomAD3 exomes

AF:

0.0167

AC:

4187

AN:

251378

Hom.:

AF XY:

0.0160

AC XY:

2179

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0187

AC:

27359

AN:

1461812

Hom.:

329

Cov.:

AF XY:

0.0183

AC XY:

13302

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0561

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0196

Gnomad4 OTH exome

AF:

0.0188

GnomAD4 genome

AF:

0.0274

AC:

4165

AN:

152230

Hom.:

108

Cov.:

AF XY:

0.0260

AC XY:

1938

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0573

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00956

Gnomad4 FIN

AF:

0.0161

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0219

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0283

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.0524

AC:

231

ESP6500EA

AF:

0.0174

AC:

150

ExAC

AF:

0.0174

AC:

2111

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0178

EpiControl

AF:

0.0151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PNPLA5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0032

T;T;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.69

.;T;T;.

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.0

M;M;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

.;N;.;D

REVEL

Benign

0.21

Sift

Benign

0.085

.;T;.;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.98

D;D;P;P

Vest4

0.084

MPC

0.37

ClinPred

0.038

GERP RS

3.1

Varity_R

0.097

gMVP

0.57

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