20-33716847-C-G

Variant names:

• chr20-33716847-C-G
• rs1074683
• NM_007238.5:c.114-2111G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXMP4	NM_007238.5	MANE Select	c.114-2111G>C		intron	N/A	NP_009169.3
	PXMP4	NM_183397.3		c.114-2111G>C		intron	N/A	NP_899634.1	Q9Y6I8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXMP4	ENST00000409299.8	TSL:1 MANE Select	c.114-2111G>C		intron	N/A	ENSP00000386385.3	Q9Y6I8-1
	PXMP4	ENST00000945198.1		c.113+3248G>C		intron	N/A	ENSP00000615257.1
	PXMP4	ENST00000217398.3	TSL:2	c.114-2111G>C		intron	N/A	ENSP00000217398.3	B4DWH1

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

African (AFR) AF: 0.220 AC: 9122 AN: 41494

American (AMR) AF: 0.325 AC: 4962 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5174

South Asian (SAS) AF: 0.176 AC: 849 AN: 4830

European-Finnish (FIN) AF: 0.233 AC: 2464 AN: 10554

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16795 AN: 67986

Other (OTH) AF: 0.241 AC: 509 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.7
DANN	Benign	0.88
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1074683;

hg19: chr20-32304653;