20-33716847-C-G

Position:

• chr20-33716847-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007238.5(PXMP4):​c.114-2111G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,080 control chromosomes in the GnomAD database, including 4,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4719 hom., cov: 31)
• Consequence: PXMP4 NM_007238.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXMP4	NM_007238.5	c.114-2111G>C		intron_variant		ENST00000409299.8
PXMP4	NM_183397.3	c.114-2111G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXMP4	ENST00000409299.8	c.114-2111G>C		intron_variant		1	NM_007238.5	P1
PXMP4	ENST00000217398.3	c.114-2111G>C		intron_variant		2
PXMP4	ENST00000344022.7	c.114-2111G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37053 AN: 151962 Hom.: 4712 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37086 AN: 152080 Hom.: 4719 Cov.: 31 AF XY: 0.244 AC XY: 18102 AN XY: 74324

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.241

Alfa AF: 0.148 Hom.: 269

Bravo AF: 0.254

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.7
DANN	Benign	0.88

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

Other links and lift over

dbSNP: rs1074683; hg19: chr20-32304653;