20-33710716-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007238.5(PXMP4):​c.214T>G​(p.Tyr72Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

PXMP4
NM_007238.5 missense

Scores

1
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34
Variant links:
Genes affected
PXMP4 (HGNC:15920): (peroxisomal membrane protein 4) Located in peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19435555).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXMP4NM_007238.5 linkuse as main transcriptc.214T>G p.Tyr72Asp missense_variant 3/4 ENST00000409299.8
PXMP4NM_183397.3 linkuse as main transcriptc.177-2747T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXMP4ENST00000409299.8 linkuse as main transcriptc.214T>G p.Tyr72Asp missense_variant 3/41 NM_007238.5 P1Q9Y6I8-1
PXMP4ENST00000217398.3 linkuse as main transcriptc.234T>G p.His78Gln missense_variant 3/42
PXMP4ENST00000344022.7 linkuse as main transcriptc.177-2747T>G intron_variant 2 Q9Y6I8-2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
30

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 01, 2023The c.214T>G (p.Y72D) alteration is located in exon 3 (coding exon 3) of the PXMP4 gene. This alteration results from a T to G substitution at nucleotide position 214, causing the tyrosine (Y) at amino acid position 72 to be replaced by an aspartic acid (D). 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
Uncertain
0.53
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Benign
0.84
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.13
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.16
T
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
D;D;N
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.31
Sift
Benign
0.046
D
Sift4G
Uncertain
0.058
T
Polyphen
0.30
B
Vest4
0.18
MutPred
0.35
Loss of disorder (P = 0.2041);
MVP
0.068
ClinPred
0.96
D
GERP RS
4.1

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.

Other links and lift over

hg19: chr20-32298522; API