rs773922257

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_000466.3(PEX1):c.665C>T(p.Thr222Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,543,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PEX1
NM_000466.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

PEX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09309521).

BP6

Variant 7-92517850-G-A is Benign according to our data. Variant chr7-92517850-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197673.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3 link	c.665C>T	p.Thr222Ile	missense_variant	Exon 5 of 24	ENST00000248633.9	NP_000457.1	O43933-1
PEX1	NM_001282677.2 link	c.665C>T	p.Thr222Ile	missense_variant	Exon 5 of 23		NP_001269606.1	O43933A0A0C4DG33
PEX1	NM_001282678.2 link	c.41C>T	p.Thr14Ile	missense_variant	Exon 5 of 24		NP_001269607.1	O43933B4DER6
PEX1	XM_047420472.1 link	c.665C>T	p.Thr222Ile	missense_variant	Exon 5 of 23		XP_047276428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX1	ENST00000248633.9 link	c.665C>T	p.Thr222Ile	missense_variant	Exon 5 of 24	1	NM_000466.3	ENSP00000248633.4	O43933-1
PEX1	ENST00000428214.5 link	c.665C>T	p.Thr222Ile	missense_variant	Exon 5 of 23	1		ENSP00000394413.1	A0A0C4DG33
PEX1	ENST00000438045.5 link	c.274-3883C>T		intron_variant	Intron 2 of 20	2		ENSP00000410438.1	O43933-2
PEX1	ENST00000484913.5 link	n.704C>T		non_coding_transcript_exon_variant	Exon 5 of 24	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000525

AC:

AN:

190414

Hom.:

AF XY:

0.00

AC XY:

AN XY:

101000

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1390812

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

685802

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:

0.0000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 12, 2014

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder 1B;C4551980:Heimler syndrome 1;C4721541:Peroxisome biogenesis disorder 1A (Zellweger)

Uncertain:1

Oct 31, 2018

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Zellweger spectrum disorders

Benign:1

Nov 24, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.052

T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.093

T;T

MetaSVM

Uncertain

-0.089

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.16

Sift

Benign

0.052

T;D

Sift4G

Benign

0.20

T;T

Polyphen

0.23

B;.

Vest4

0.26

MVP

0.80

MPC

0.18

ClinPred

0.072

GERP RS

3.1

Varity_R

0.055

gMVP

0.15

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