6-136822610-C-T

Variant summary

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

The NM_000288.4(PEX7):c.-56C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 1,486,664 control chromosomes in the GnomAD database, including 4,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2125 hom., cov: 35)

Exomes 𝑓: 0.038 ( 2305 hom. )

Consequence

PEX7
NM_000288.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.377

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:

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=-0.73).

BP6

Variant 6-136822610-C-T is Benign according to our data. Variant chr6-136822610-C-T is described in ClinVar as [Benign]. Clinvar id is 355522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PEX7	NM_000288.4 linkuse as main transcript	c.-56C>T	5_prime_UTR_variant	1/10	ENST00000318471.5
PEX7	XM_006715502.3 linkuse as main transcript	c.-56C>T	5_prime_UTR_variant	1/7
PEX7	XM_047418874.1 linkuse as main transcript	c.-56C>T	5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX7	ENST00000318471.5 linkuse as main transcript	c.-56C>T	5_prime_UTR_variant	1/10	1	NM_000288.4	P1	O00628-1
PEX7	ENST00000367756.8 linkuse as main transcript	c.-56C>T	5_prime_UTR_variant	1/4	3
PEX7	ENST00000541292.6 linkuse as main transcript	c.-56C>T	5_prime_UTR_variant, NMD_transcript_variant	1/11	5			O00628-2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16720

AN:

152170

Hom.:

2123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0612

Gnomad ASJ

AF:

0.0475

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0923

GnomAD4 exome

AF:

0.0380

AC:

50715

AN:

1334376

Hom.:

2305

Cov.:

AF XY:

0.0362

AC XY:

23915

AN XY:

660774

show subpopulations

Gnomad4 AFR exome

AF:

0.322

Gnomad4 AMR exome

AF:

0.0415

Gnomad4 ASJ exome

AF:

0.0456

Gnomad4 EAS exome

AF:

0.0000579

Gnomad4 SAS exome

AF:

0.00665

Gnomad4 FIN exome

AF:

0.0161

Gnomad4 NFE exome

AF:

0.0332

Gnomad4 OTH exome

AF:

0.0508

GnomAD4 genome

AF:

0.110

AC:

16744

AN:

152288

Hom.:

2125

Cov.:

AF XY:

0.106

AC XY:

7869

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.0611

Gnomad4 ASJ

AF:

0.0475

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00724

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.0346

Gnomad4 OTH

AF:

0.0908

Alfa

AF:

0.0629

Hom.:

177

Bravo

AF:

0.122

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 14, 2016	- -
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. -

Rhizomelic chondrodysplasia punctata type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Peroxisome biogenesis disorder 9B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Rhizomelic chondrodysplasia punctata

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

Cadd

Benign

8.1

Dann

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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