3-179859136-G-C

Variant names:

• chr3-179859136-G-C
• rs759355045
• NM_016559.3:c.748C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016559.3(PEX5L):​c.748C>G​(p.Arg250Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEX5L NM_016559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX5L	NM_016559.3	c.748C>G	p.Arg250Gly	missense_variant	Exon 8 of 15	ENST00000467460.6	NP_057643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX5L	ENST00000467460.6	c.748C>G	p.Arg250Gly	missense_variant	Exon 8 of 15	1	NM_016559.3	ENSP00000419975.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.748C>G (p.R250G) alteration is located in exon 8 (coding exon 8) of the PEX5L gene. This alteration results from a C to G substitution at nucleotide position 748, causing the arginine (R) at amino acid position 250 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;.;.;.;.;.;.;.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;.;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	2.0	.;M;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.57	N;N;N;N;N;N;N;N;N;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.46	T;T;T;T;T;T;T;T;T;.
Polyphen		0.99, 1.0, 0.99	.;D;D;D;.;.;.;.;.;.
Vest4		0.63
MutPred		0.38		.;Gain of glycosylation at T246 (P = 0.0122);.;.;.;.;.;.;.;.;
MVP		0.92
MPC		1.4
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.43
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759355045; hg19: chr3-179576924;