rs9856007

chr3-180024949-T-C

Variant summary

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

The NM_016559.3(PEX5L):c.21+11630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,978 control chromosomes in the GnomAD database, including 12,340 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 0.37 (12340 hom., cov: 31)
• Consequence: PEX5L NM_016559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX5L	NM_016559.3	c.21+11630A>G		intron_variant		ENST00000467460.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX5L	ENST00000467460.6	c.21+11630A>G		intron_variant		1	NM_016559.3	A1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55643 AN: 151860 Hom.: 12309 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.367 AC: 55717 AN: 151978 Hom.: 12340 Cov.: 31 AF XY: 0.361 AC XY: 26835 AN XY: 74296

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.310

Alfa AF: 0.334 Hom.: 2263

Bravo AF: 0.369

Asia WGS AF: 0.260 AC: 905 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	10
Dann	Benign	0.66

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: rs9856007; hg19: chr3-179742737;