20-33710716-A-C

Position:

• chr20-33710716-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.34

Genes affected

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

ACMG classification

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
PXMP4	NM_007238.5	c.214T>G	p.Tyr72Asp	missense_variant	3/4	ENST00000409299.8
PXMP4	NM_183397.3	c.177-2747T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXMP4	ENST00000409299.8	c.214T>G	p.Tyr72Asp	missense_variant	3/4	1	NM_007238.5	P1
PXMP4	ENST00000217398.3	c.234T>G	p.His78Gln	missense_variant	3/4	2
PXMP4	ENST00000344022.7	c.177-2747T>G		intron_variant		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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 01, 2023

The 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;