Variant 22-43889331-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000216177.9(PNPLA5):c.700G>A(p.Glu234Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

PNPLA5
ENST00000216177.9 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08386293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PNPLA5	NM_138814.4 linkuse as main transcript	c.700G>A	p.Glu234Lys	missense_variant, splice_region_variant	4/9	ENST00000216177.9	NP_620169.1
PNPLA5	NM_001177675.2 linkuse as main transcript	c.358G>A	p.Glu120Lys	missense_variant, splice_region_variant	2/7		NP_001171146.1
PNPLA5	NM_001371410.1 linkuse as main transcript	c.280G>A	p.Glu94Lys	missense_variant, splice_region_variant	4/9		NP_001358339.1
PNPLA5	XM_047441164.1 linkuse as main transcript	c.280G>A	p.Glu94Lys	missense_variant, splice_region_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.700G>A	p.Glu234Lys	missense_variant, splice_region_variant	4/9	1	NM_138814.4	ENSP00000216177	P1	Q7Z6Z6-1
PNPLA5	ENST00000381198.7 linkuse as main transcript	c.358G>A	p.Glu120Lys	missense_variant, splice_region_variant	2/7	2		ENSP00000370595		Q7Z6Z6-2
PNPLA5	ENST00000438734.1 linkuse as main transcript	c.427-1680G>A		intron_variant		3		ENSP00000405732

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250682

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000724

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000763

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.00000824

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

Jul 19, 2022

The c.700G>A (p.E234K) alteration is located in exon 4 (coding exon 4) of the PNPLA5 gene. This alteration results from a G to A substitution at nucleotide position 700, causing the glutamic acid (E) at amino acid position 234 to be replaced by a lysine (K). 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

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0027

T;T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.71

.;T;T;.

M_CAP

Benign

0.054

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

0.79

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

0.34

.;N;.;N

REVEL

Benign

0.049

Sift

Benign

1.0

.;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.95

P;P;B;B

Vest4

0.17

MVP

0.48

MPC

0.46

ClinPred

0.097

GERP RS

2.8

Varity_R

0.081

gMVP

0.63

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