Variant 6-136822725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_000288.4(PEX7):c.60C>T(p.Tyr20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,361,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

PEX7
NM_000288.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.207

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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 6-136822725-C-T is Benign according to our data. Variant chr6-136822725-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1088151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.207 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PEX7	NM_000288.4 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant	1/10	ENST00000318471.5
PEX7	XM_006715502.3 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant	1/7
PEX7	XM_047418874.1 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX7	ENST00000318471.5 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant	1/10	1	NM_000288.4	P1	O00628-1
PEX7	ENST00000367756.8 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant	1/4	3
PEX7	ENST00000541292.6 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant, NMD_transcript_variant	1/11	5			O00628-2
PEX7	ENST00000678593.1 linkuse as main transcript	c.60C>T	p.Tyr20=	synonymous_variant, NMD_transcript_variant	1/8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1361810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.35e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2020

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Peroxisome biogenesis disorder 9B

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over