1-160277395-G-C

Position:

chr1-160277395-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000368072.10(PEX19):c.*2156C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 455,818 control chromosomes in the GnomAD database, including 56,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16145 hom., cov: 32)

Exomes 𝑓: 0.51 ( 39923 hom. )

Consequence

PEX19
ENST00000368072.10 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.465

Variant links:

Genes affected

PEX19 (HGNC:9713): (peroxisomal biogenesis factor 19) This gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. These disorders have at least 14 complementation groups, with more than one phenotype being observed for some complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause of Zellweger syndrome (ZWS), as well as peroxisome biogenesis disorder complementation group 14 (PBD-CG14), which is also known as PBD-CGJ. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

PEX19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-160277395-G-C is Benign according to our data. Variant chr1-160277395-G-C is described in ClinVar as [Benign]. Clinvar id is 293196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PEX19	NM_002857.4 linkuse as main transcript	c.*2156C>G	3_prime_UTR_variant	8/8	ENST00000368072.10	NP_002848.1
PEX19	NM_001193644.1 linkuse as main transcript	c.*2164C>G	3_prime_UTR_variant	8/8		NP_001180573.1
PEX19	NR_036492.2 linkuse as main transcript	n.2955C>G	non_coding_transcript_exon_variant	7/7
PEX19	NR_036493.2 linkuse as main transcript	n.2979C>G	non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX19	ENST00000368072.10 linkuse as main transcript	c.*2156C>G	3_prime_UTR_variant	8/8	1	NM_002857.4	ENSP00000357051	P1	P40855-1
PEX19	ENST00000472750.5 linkuse as main transcript	c.*2823C>G	3_prime_UTR_variant, NMD_transcript_variant	7/7	1		ENSP00000434633		P40855-6
PEX19	ENST00000467711.5 linkuse as main transcript	n.120-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69175

AN:

151946

Hom.:

16142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.482

GnomAD3 exomes

AF:

0.495

AC:

63464

AN:

128218

Hom.:

16141

AF XY:

0.503

AC XY:

35291

AN XY:

70226

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.348

Gnomad SAS exome

AF:

0.615

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.507

AC:

154061

AN:

303754

Hom.:

39923

Cov.:

AF XY:

0.518

AC XY:

89580

AN XY:

172980

show subpopulations

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.483

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.490

GnomAD4 genome

AF:

0.455

AC:

69214

AN:

152064

Hom.:

16145

Cov.:

AF XY:

0.456

AC XY:

33905

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.477

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.346

Gnomad4 SAS

AF:

0.609

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.466

Hom.:

3007

Bravo

AF:

0.448

Asia WGS

AF:

0.477

AC:

1657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Peroxisome biogenesis disorder 12A (Zellweger)

Benign:1

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

-0.88

CADD

Benign

2.1

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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