chr20-33707762-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007238.5(PXMP4):​c.583G>A​(p.Val195Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PXMP4
NM_007238.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.727
Variant links:
Genes affected
PXMP4 (HGNC:15920): (peroxisomal membrane protein 4) Located in peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033673227).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXMP4NM_007238.5 linkuse as main transcriptc.583G>A p.Val195Ile missense_variant 4/4 ENST00000409299.8
PXMP4NM_183397.3 linkuse as main transcriptc.*168G>A 3_prime_UTR_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXMP4ENST00000409299.8 linkuse as main transcriptc.583G>A p.Val195Ile missense_variant 4/41 NM_007238.5 P1Q9Y6I8-1
PXMP4ENST00000217398.3 linkuse as main transcriptc.*168G>A 3_prime_UTR_variant 4/42
PXMP4ENST00000344022.7 linkuse as main transcriptc.*168G>A 3_prime_UTR_variant 3/32 Q9Y6I8-2

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152200
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000603
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251472
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000308
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:
0.00000547
AC:
8
AN:
1461876
Hom.:
0
Cov.:
33
AF XY:
0.00000825
AC XY:
6
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
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:
0.0000166
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152318
Hom.:
0
Cov.:
31
AF XY:
0.000134
AC XY:
10
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.000601
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000174
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsFeb 17, 2023The c.583G>A (p.V195I) alteration is located in exon 4 (coding exon 4) of the PXMP4 gene. This alteration results from a G to A substitution at nucleotide position 583, causing the valine (V) at amino acid position 195 to be replaced by an isoleucine (I). 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
0.076
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
10
DANN
Uncertain
0.98
DEOGEN2
Benign
0.044
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D;D;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.53
N
REVEL
Benign
0.067
Sift
Benign
0.41
T
Sift4G
Benign
0.41
T
Polyphen
0.038
B
Vest4
0.091
MVP
0.21
MPC
0.48
ClinPred
0.092
T
GERP RS
5.8
Varity_R
0.050
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.

Other links and lift over

dbSNP: rs145235084; hg19: chr20-32295568; API