6-36293081-C-T

Position:

chr6-36293081-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001374623.1(PNPLA1):c.459C>T(p.Phe153Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,612,774 control chromosomes in the GnomAD database, including 121,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14009 hom., cov: 31)

Exomes 𝑓: 0.38 ( 107332 hom. )

Consequence

PNPLA1
NM_001374623.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 6-36293081-C-T is Benign according to our data. Variant chr6-36293081-C-T is described in ClinVar as [Benign]. Clinvar id is 257572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-36293081-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA1	NM_001374623.1 linkuse as main transcript	c.459C>T	p.Phe153Phe	synonymous_variant	3/9	ENST00000636260.2	NP_001361552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA1	ENST00000636260.2 linkuse as main transcript	c.459C>T	p.Phe153Phe	synonymous_variant	3/9	5	NM_001374623.1	ENSP00000490785.2		A0A1B0GW56
PNPLA1	ENST00000457797.5 linkuse as main transcript	c.462C>T	p.Phe154Phe	synonymous_variant	3/8	1		ENSP00000391868.1		A0A0C4DG24

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

63951

AN:

151720

Hom.:

13992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.449

GnomAD3 exomes

AF:

0.371

AC:

93102

AN:

250940

Hom.:

18226

AF XY:

0.372

AC XY:

50490

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.354

Gnomad SAS exome

AF:

0.335

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.379

AC:

554323

AN:

1460936

Hom.:

107332

Cov.:

AF XY:

0.380

AC XY:

276218

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.536

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.484

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.422

AC:

64002

AN:

151838

Hom.:

14009

Cov.:

AF XY:

0.417

AC XY:

30919

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.485

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.403

Hom.:

16657

Bravo

AF:

0.424

Asia WGS

AF:

0.408

AC:

1421

AN:

3478

EpiCase

AF:

0.400

EpiControl

AF:

0.405

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Autosomal recessive congenital ichthyosis 10

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

5.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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