Variant 22-43886427-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_138814.4(PNPLA5):c.825C>T(p.Asp275Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,612,920 control chromosomes in the GnomAD database, including 137,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.37 ( 11859 hom., cov: 32)

Exomes 𝑓: 0.40 ( 125319 hom. )

Consequence

PNPLA5
NM_138814.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.25

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-43886427-G-A is Benign according to our data. Variant chr22-43886427-G-A is described in ClinVar as [Benign]. Clinvar id is 3059962.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA5	NM_138814.4 linkuse as main transcript	c.825C>T	p.Asp275Asp	synonymous_variant	6/9	ENST00000216177.9	NP_620169.1	Q7Z6Z6-1
PNPLA5	NM_001177675.2 linkuse as main transcript	c.483C>T	p.Asp161Asp	synonymous_variant	4/7		NP_001171146.1	Q7Z6Z6-2
PNPLA5	NM_001371410.1 linkuse as main transcript	c.405C>T	p.Asp135Asp	synonymous_variant	6/9		NP_001358339.1
PNPLA5	XM_047441164.1 linkuse as main transcript	c.405C>T	p.Asp135Asp	synonymous_variant	4/7		XP_047297120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PNPLA5	ENST00000216177.9 linkuse as main transcript	c.825C>T	p.Asp275Asp	synonymous_variant	6/9	1	NM_138814.4	ENSP00000216177.3	Q7Z6Z6-1
PNPLA5	ENST00000381198.7 linkuse as main transcript	c.483C>T	p.Asp161Asp	synonymous_variant	4/7	2		ENSP00000370595.2	Q7Z6Z6-2
PNPLA5	ENST00000438734.1 linkuse as main transcript	c.549C>T	p.Asp183Asp	synonymous_variant	4/5	3		ENSP00000405732.1	B1AHL9

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56693

AN:

151964

Hom.:

11858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.447

AC:

112203

AN:

250734

Hom.:

28414

AF XY:

0.453

AC XY:

61386

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.469

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.931

Gnomad SAS exome

AF:

0.578

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.399

AC:

582770

AN:

1460838

Hom.:

125319

Cov.:

AF XY:

0.405

AC XY:

294429

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.463

Gnomad4 ASJ exome

AF:

0.358

Gnomad4 EAS exome

AF:

0.932

Gnomad4 SAS exome

AF:

0.579

Gnomad4 FIN exome

AF:

0.402

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.373

AC:

56707

AN:

152082

Hom.:

11859

Cov.:

AF XY:

0.381

AC XY:

28315

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.429

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.926

Gnomad4 SAS

AF:

0.605

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.375

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.372

Hom.:

14018

Bravo

AF:

0.367

Asia WGS

AF:

0.720

AC:

2498

AN:

3478

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

Oct 17, 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

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.44

DANN

Benign

0.32

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