chr3-180024949-T-C

Variant names:

• chr3-180024949-T-C
• rs9856007
• NM_016559.3:c.21+11630A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000287645 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEX5L	NM_016559.3	c.21+11630A>G		intron_variant	Intron 1 of 14	ENST00000467460.6	NP_057643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX5L	ENST00000467460.6	c.21+11630A>G		intron_variant	Intron 1 of 14	1	NM_016559.3	ENSP00000419975.1

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

African (AFR) AF: 0.636 AC: 26360 AN: 41430

American (AMR) AF: 0.224 AC: 3425 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3468

East Asian (EAS) AF: 0.161 AC: 833 AN: 5174

South Asian (SAS) AF: 0.309 AC: 1488 AN: 4814

European-Finnish (FIN) AF: 0.280 AC: 2959 AN: 10576

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18926 AN: 67920

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.340 Hom.: 2426

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
PhyloP100		1.4
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

Other links and lift over

dbSNP: rs9856007; hg19: chr3-179742737;