rs9842394

Positions:

• chr3-179895448-C-T

Variant summary

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

The ENST00000467460.6(PEX5L):​c.198+2694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,894 control chromosomes in the GnomAD database, including 13,069 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 0.41 (13069 hom., cov: 32)
• Consequence: PEX5L ENST00000467460.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

Genes affected

PEX5L (HGNC:30024): (peroxisomal biogenesis factor 5 like) Enables peroxisome matrix targeting signal-1 binding activity and small GTPase binding activity. Predicted to be involved in protein import into peroxisome matrix, docking and regulation of cAMP-mediated signaling. Predicted to act upstream of or within maintenance of protein location and regulation of membrane potential. Located in cytosol. Part of receptor complex. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX5L	NM_016559.3	c.198+2694G>A		intron_variant		ENST00000467460.6	NP_057643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX5L	ENST00000467460.6	c.198+2694G>A		intron_variant		1	NM_016559.3	ENSP00000419975	A1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61840 AN: 151776 Hom.: 13049 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.408 AC: 61900 AN: 151894 Hom.: 13069 Cov.: 32 AF XY: 0.401 AC XY: 29741 AN XY: 74234

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.407

Alfa AF: 0.449 Hom.: 7349

Bravo AF: 0.395

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.44

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: rs9842394; hg19: chr3-179613236;