6-136822610-C-T

Variant names:

• chr6-136822610-C-T
• rs73777751
• NM_000288.4:c.-56C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.377

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX7	NM_000288.4	c.-56C>T		5_prime_UTR_variant	Exon 1 of 10	ENST00000318471.5	NP_000279.1
PEX7	XM_006715502.3	c.-56C>T		5_prime_UTR_variant	Exon 1 of 7		XP_006715565.1
PEX7	XM_047418874.1	c.-56C>T		5_prime_UTR_variant	Exon 1 of 6		XP_047274830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX7	ENST00000318471	c.-56C>T		5_prime_UTR_variant	Exon 1 of 10	1	NM_000288.4	ENSP00000315680.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16720 AN: 152170 Hom.: 2123 Cov.: 35

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.: 24 AF XY: 0.0362 AC XY: 23915 AN XY: 660774

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.: 35 AF XY: 0.106 AC XY: 7869 AN XY: 74484

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: 87 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 14, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Rhizomelic chondrodysplasia punctata Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs73777751; hg19: chr6-137143748;