rs9825224

Positions:

• chr3-179957766-C-A
• chr3-179957766-C-G
• chr3-179957766-C-T

Variant summary

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

The NM_016559.3(PEX5L):​c.93+13828G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,112 control chromosomes in the GnomAD database, including 39,598 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 0.72 (39598 hom., cov: 32)
• Consequence: PEX5L NM_016559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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]

LOC124909463 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX5L	NM_016559.3	c.93+13828G>T		intron_variant		ENST00000467460.6
LOC124909463	XR_007096182.1	n.123+906C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX5L	ENST00000467460.6	c.93+13828G>T		intron_variant		1	NM_016559.3	A1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109355 AN: 151994 Hom.: 39564 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.719 AC: 109441 AN: 152112 Hom.: 39598 Cov.: 32 AF XY: 0.722 AC XY: 53668 AN XY: 74344

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.713

Alfa AF: 0.705 Hom.: 49364

Bravo AF: 0.718

Asia WGS AF: 0.840 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.64

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: rs9825224; hg19: chr3-179675554;