Variant 22-43886441-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138814.4(PNPLA5):c.811C>T(p.Pro271Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PNPLA5
NM_138814.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.438

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=0.113577455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA5	NM_138814.4 linkuse as main transcript	c.811C>T	p.Pro271Ser	missense_variant	6/9	ENST00000216177.9	NP_620169.1	Q7Z6Z6-1
PNPLA5	NM_001177675.2 linkuse as main transcript	c.469C>T	p.Pro157Ser	missense_variant	4/7		NP_001171146.1	Q7Z6Z6-2
PNPLA5	NM_001371410.1 linkuse as main transcript	c.391C>T	p.Pro131Ser	missense_variant	6/9		NP_001358339.1
PNPLA5	XM_047441164.1 linkuse as main transcript	c.391C>T	p.Pro131Ser	missense_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.811C>T	p.Pro271Ser	missense_variant	6/9	1	NM_138814.4	ENSP00000216177.3	Q7Z6Z6-1
PNPLA5	ENST00000381198.7 linkuse as main transcript	c.469C>T	p.Pro157Ser	missense_variant	4/7	2		ENSP00000370595.2	Q7Z6Z6-2
PNPLA5	ENST00000438734.1 linkuse as main transcript	c.535C>T	p.Pro179Ser	missense_variant	4/5	3		ENSP00000405732.1	B1AHL9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 12, 2022

The c.811C>T (p.P271S) alteration is located in exon 6 (coding exon 6) of the PNPLA5 gene. This alteration results from a C to T substitution at nucleotide position 811, causing the proline (P) at amino acid position 271 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.2

DANN

Benign

0.97

DEOGEN2

Benign

0.0059

T;T;.;.;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.64

.;T;T;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.5

L;L;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.6

.;D;.;D;D

REVEL

Benign

0.11

Sift

Benign

0.16

.;T;.;T;T

Sift4G

Benign

0.35

T;T;T;T;.

Polyphen

0.051

B;B;P;P;.

Vest4

0.097

MutPred

0.34

Loss of catalytic residue at P270 (P = 0.0193);Loss of catalytic residue at P270 (P = 0.0193);.;.;.;

MVP

0.53

MPC

0.19

ClinPred

0.26

GERP RS

1.6

Varity_R

0.077

gMVP

0.22

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