rs7630877

Positions:

• chr3-179943530-G-A
• chr3-179943530-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016559.3(PEX5L):​c.93+28064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,040 control chromosomes in the GnomAD database, including 8,425 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 0.33 (8425 hom., cov: 33)
• Consequence: PEX5L NM_016559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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]

PEX5L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX5L	NM_016559.3	c.93+28064C>T		intron_variant		ENST00000467460.6	NP_057643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX5L	ENST00000467460.6	c.93+28064C>T		intron_variant		1	NM_016559.3	ENSP00000419975.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50032 AN: 151922 Hom.: 8409 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.329 AC: 50071 AN: 152040 Hom.: 8425 Cov.: 33 AF XY: 0.328 AC XY: 24353 AN XY: 74304

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.351

Alfa AF: 0.336 Hom.: 19772

Bravo AF: 0.320

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.4
DANN	Benign	0.68

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: rs7630877; hg19: chr3-179661318;