Variant 20-33710746-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007238.5(PXMP4):c.184G>A(p.Glu62Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,450,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PXMP4
NM_007238.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

PXMP4 (HGNC:15920): (peroxisomal membrane protein 4) Located in peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

PXMP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2709989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXMP4	NM_007238.5 linkuse as main transcript	c.184G>A	p.Glu62Lys	missense_variant	3/4	ENST00000409299.8	NP_009169.3	Q9Y6I8-1
PXMP4	NM_183397.3 linkuse as main transcript	c.177-2777G>A		intron_variant			NP_899634.1	Q9Y6I8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PXMP4	ENST00000409299.8 linkuse as main transcript	c.184G>A	p.Glu62Lys	missense_variant	3/4	1	NM_007238.5	ENSP00000386385.3	Q9Y6I8-1
PXMP4	ENST00000217398.3 linkuse as main transcript	c.204G>A	p.Arg68Arg	synonymous_variant	3/4	2		ENSP00000217398.3	B4DWH1
PXMP4	ENST00000344022.7 linkuse as main transcript	c.177-2777G>A		intron_variant		2		ENSP00000343071.3	Q9Y6I8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000421

AC:

AN:

237660

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129094

show subpopulations

Gnomad AFR exome

AF:

0.0000642

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:

6.90e-7

AC:

AN:

1450280

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.184G>A (p.E62K) alteration is located in exon 3 (coding exon 3) of the PXMP4 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the glutamic acid (E) at amino acid position 62 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

Eigen

Benign

0.12

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Benign

0.021

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

REVEL

Benign

0.12

Sift

Benign

0.060

Sift4G

Benign

0.20

Polyphen

0.44

Vest4

0.21

MutPred

0.54

Gain of MoRF binding (P = 0.0041);

MVP

0.23

MPC

0.75

ClinPred

0.48

GERP RS

4.3

Varity_R

0.12

gMVP

0.46

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