Variant 6-36270652-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_001374623.1(PNPLA1):c.193G>A(p.Gly65Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000058 in 1,550,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

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

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

PNPLA1
NM_001374623.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.93

Variant links:

Genes affected

PNPLA1 (HGNC:21246): (patatin like phospholipase domain containing 1) The protein encoded by this gene belongs to the patatin-like phospholipase (PNPLA) family, which is characterized by the presence of a highly conserved patatin domain. PNPLA family members have diverse lipolytic and acyltransferase activities, and are key elements in lipid metabolism. While other members of this family have been well characterized, the function of this gene remained an enigma. However, recent studies show that this gene is expressed in the skin epidermal keratinocytes, and has a role in glycerophospholipid metabolism in the cutaneous barrier. Consistent with these observations, mutations in this gene are associated with ichthyosis in human (autosomal recessive congenital ichthyoses, ARCI) and dog. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

PNPLA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 6-36270652-G-A is Benign according to our data. Variant chr6-36270652-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2681493.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA1	NM_001374623.1 linkuse as main transcript	c.193G>A	p.Gly65Arg	missense_variant	1/9	ENST00000636260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA1	ENST00000636260.2 linkuse as main transcript	c.193G>A	p.Gly65Arg	missense_variant	1/9	5	NM_001374623.1	A2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000263

AC:

AN:

152150

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

80990

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000920

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1398660

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689886

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma

Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.082

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

0.94

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.4

D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.99

.;D

Vest4

0.55

MutPred

0.79

Loss of catalytic residue at C64 (P = 0.0702);Loss of catalytic residue at C64 (P = 0.0702);

MVP

0.89

MPC

0.80

ClinPred

0.54

GERP RS

4.3

Varity_R

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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