Genetic Variant NM_002857.4:c.*1471A>T (chr1-160278080-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002857.4(PEX19):c.*1471A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 702,516 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 28 hom. )

Consequence

PEX19
NM_002857.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.421

Publications

2 publications found

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:

ENSG00000258465 (HGNC:):

ENSG00000258465 links:

DCAF8-DT (HGNC:55792): (DCAF8 divergent transcript)

DCAF8-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-160278080-T-A is Benign according to our data. Variant chr1-160278080-T-A is described in ClinVar as Benign. ClinVar VariationId is 874148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0018 (274/152298) while in subpopulation EAS AF = 0.0268 (139/5186). AF 95% confidence interval is 0.0232. There are 4 homozygotes in GnomAd4. There are 142 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002857.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX19	NM_002857.4	MANE Select	c.*1471A>T	3_prime_UTR	Exon 8 of 8	NP_002848.1	A0A0S2Z497
PEX19	NM_001193644.1		c.*1479A>T	3_prime_UTR	Exon 8 of 8	NP_001180573.1	P40855
PEX19	NR_036492.2		n.2270A>T	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PEX19	ENST00000368072.10	TSL:1 MANE Select	c.*1471A>T	3_prime_UTR	Exon 8 of 8	ENSP00000357051.5	P40855-1
ENSG00000258465	ENST00000485079.1	TSL:3	c.487+51A>T	intron	N/A	ENSP00000450870.1	H0YJ60
PEX19	ENST00000472750.5	TSL:1	n.*2138A>T	non_coding_transcript_exon	Exon 7 of 7	ENSP00000434633.1	P40855-6

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

277

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0271

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00555

AC:

726

AN:

130796

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.000329

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.00399

GnomAD4 exome

AF:

0.00375

AC:

2064

AN:

550218

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

946

AN XY:

297842

show subpopulations

African (AFR)

AF:

0.000696

AC:

AN:

15806

American (AMR)

AF:

0.0171

AC:

595

AN:

34714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20026

East Asian (EAS)

AF:

0.0425

AC:

1363

AN:

32100

South Asian (SAS)

AF:

0.000350

AC:

AN:

62774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33182

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.0000726

AC:

AN:

316942

Other (OTH)

AF:

0.00160

AC:

AN:

30600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

130

261

391

522

652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00180

AC:

274

AN:

152298

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000867

AC:

AN:

41546

American (AMR)

AF:

0.00497

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0268

AC:

139

AN:

5186

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000726

Hom.:

Bravo

AF:

0.00286

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Peroxisome biogenesis disorder 12A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

(source)

DANN

Benign

0.68

PhyloP100

-0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over