Variant 22-43886297-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000216177.9(PNPLA5):c.949+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,609,490 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 6 hom. )

Consequence

PNPLA5
ENST00000216177.9 splice_donor_region, intron

Scores

Splicing: ADA: 0.0001306

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.927

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 22-43886297-C-A is Benign according to our data. Variant chr22-43886297-C-A is described in ClinVar as [Benign]. Clinvar id is 3035582.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PNPLA5	NM_138814.4 linkuse as main transcript	c.949+6G>T	splice_donor_region_variant, intron_variant	ENST00000216177.9	NP_620169.1
PNPLA5	NM_001177675.2 linkuse as main transcript	c.607+6G>T	splice_donor_region_variant, intron_variant		NP_001171146.1
PNPLA5	NM_001371410.1 linkuse as main transcript	c.529+6G>T	splice_donor_region_variant, intron_variant		NP_001358339.1
PNPLA5	XM_047441164.1 linkuse as main transcript	c.529+6G>T	splice_donor_region_variant, intron_variant		XP_047297120.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
PNPLA5	ENST00000216177.9 linkuse as main transcript	c.949+6G>T	splice_donor_region_variant, intron_variant	1	NM_138814.4	ENSP00000216177	P1	Q7Z6Z6-1
PNPLA5	ENST00000381198.7 linkuse as main transcript	c.607+6G>T	splice_donor_region_variant, intron_variant	2		ENSP00000370595		Q7Z6Z6-2
PNPLA5	ENST00000438734.1 linkuse as main transcript	c.673+6G>T	splice_donor_region_variant, intron_variant	3		ENSP00000405732

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00154

AC:

381

AN:

247632

Hom.:

AF XY:

0.00147

AC XY:

197

AN XY:

133698

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000640

AC:

933

AN:

1457200

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

460

AN XY:

724264

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000631

GnomAD4 genome

AF:

0.00133

AC:

203

AN:

152290

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

144

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0152

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000178

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

Aug 01, 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

-0.77

CADD

Benign

9.5

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.14

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