Variant chr20-33720120-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007238.5(PXMP4):c.88C>T(p.Leu30Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PXMP4
NM_007238.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.553

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXMP4	NM_007238.5 linkuse as main transcript	c.88C>T	p.Leu30Phe	missense_variant	1/4	ENST00000409299.8
PXMP4	NM_183397.3 linkuse as main transcript	c.88C>T	p.Leu30Phe	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXMP4	ENST00000409299.8 linkuse as main transcript	c.88C>T	p.Leu30Phe	missense_variant	1/4	1	NM_007238.5	P1	Q9Y6I8-1
PXMP4	ENST00000217398.3 linkuse as main transcript	c.88C>T	p.Leu30Phe	missense_variant	1/4	2
PXMP4	ENST00000344022.7 linkuse as main transcript	c.88C>T	p.Leu30Phe	missense_variant	1/3	2			Q9Y6I8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249696

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461348

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726986

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:

0.00000180

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

Feb 06, 2024

The c.88C>T (p.L30F) alteration is located in exon 1 (coding exon 1) of the PXMP4 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the leucine (L) at amino acid position 30 to be replaced by a phenylalanine (F). 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

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Pathogenic

3.2

M;M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.92

P;.;D

Vest4

0.53

MutPred

0.69

Gain of methylation at K31 (P = 0.0287);Gain of methylation at K31 (P = 0.0287);Gain of methylation at K31 (P = 0.0287);

MVP

0.45

MPC

0.91

ClinPred

0.57

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.22

gMVP

0.72

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