Variant 6-136822571-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000541292.6(PEX7):c.-95T>C variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,144,364 control chromosomes in the GnomAD database, including 178,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19992 hom., cov: 35)

Exomes 𝑓: 0.56 ( 158223 hom. )

Consequence

PEX7
ENST00000541292.6 5_prime_UTR, NMD_transcript

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.497

Variant links:

Genes affected

PEX7 (HGNC:8860): (peroxisomal biogenesis factor 7) This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular 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 have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD). [provided by RefSeq, Oct 2008]

PEX7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	Effect	MANE	Protein
PEX7	NM_000288.4 linkuse as main transcript	upstream_gene_variant	ENST00000318471.5	NP_000279.1
PEX7	XM_006715502.3 linkuse as main transcript	upstream_gene_variant		XP_006715565.1
PEX7	XM_047418874.1 linkuse as main transcript	upstream_gene_variant		XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000541292.6 linkuse as main transcript	c.-95T>C	5_prime_UTR_variant, NMD_transcript_variant	1/11	5		ENSP00000441004		O00628-2
PEX7	ENST00000318471.5 linkuse as main transcript		upstream_gene_variant		1	NM_000288.4	ENSP00000315680	P1	O00628-1
PEX7	ENST00000367756.8 linkuse as main transcript		upstream_gene_variant		3		ENSP00000356730

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76951

AN:

152078

Hom.:

19989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.517

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.511

GnomAD4 exome

AF:

0.561

AC:

556246

AN:

992168

Hom.:

158223

Cov.:

AF XY:

0.560

AC XY:

282554

AN XY:

504782

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.572

Gnomad4 EAS exome

AF:

0.415

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.579

Gnomad4 OTH exome

AF:

0.531

GnomAD4 genome

AF:

0.506

AC:

76974

AN:

152196

Hom.:

19992

Cov.:

AF XY:

0.504

AC XY:

37529

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.575

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.517

Gnomad4 NFE

AF:

0.574

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.319

Hom.:

671

Bravo

AF:

0.502

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rhizomelic chondrodysplasia punctata type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Peroxisome biogenesis disorder 9B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.6

DANN

Benign

0.58

Splicing

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