rs9842394

Variant names:

• chr3-179895448-C-T
• rs9842394
• NM_016559.3:c.198+2694G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016559.3(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 NM_016559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• 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]

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 (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX5L	NM_016559.3	MANE Select	c.198+2694G>A		intron	N/A	NP_057643.1	Q8IYB4-1
	PEX5L	NM_001349386.2		c.363+2694G>A		intron	N/A	NP_001336315.1
	PEX5L	NM_001349387.2		c.270+2694G>A		intron	N/A	NP_001336316.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX5L	ENST00000467460.6	TSL:1 MANE Select	c.198+2694G>A		intron	N/A	ENSP00000419975.1	Q8IYB4-1
	PEX5L	ENST00000263962.12	TSL:1	c.192+2694G>A		intron	N/A	ENSP00000263962.8	Q8IYB4-2
	PEX5L	ENST00000485199.5	TSL:1	c.94-7664G>A		intron	N/A	ENSP00000418440.1	Q8IYB4-3

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

African (AFR) AF: 0.361 AC: 14924 AN: 41398

American (AMR) AF: 0.305 AC: 4645 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3468

East Asian (EAS) AF: 0.147 AC: 759 AN: 5178

South Asian (SAS) AF: 0.366 AC: 1763 AN: 4816

European-Finnish (FIN) AF: 0.439 AC: 4630 AN: 10542

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31884 AN: 67938

Other (OTH) AF: 0.407 AC: 860 AN: 2114

Alfa AF: 0.451 Hom.: 8188

Bravo AF: 0.395

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.44
PhyloP100		-0.099
PromoterAI		-0.0049	Neutral
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: rs9842394; hg19: chr3-179613236;