NM_016559.3:c.748C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R250C) has been classified as Uncertain significance.

• 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
• Publications: 4 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.748C>G	p.Arg250Gly	missense	Exon 8 of 15	NP_057643.1	Q8IYB4-1
	PEX5L	NM_001349386.2		c.913C>G	p.Arg305Gly	missense	Exon 9 of 16	NP_001336315.1
	PEX5L	NM_001349387.2		c.820C>G	p.Arg274Gly	missense	Exon 9 of 16	NP_001336316.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX5L	ENST00000467460.6	TSL:1 MANE Select	c.748C>G	p.Arg250Gly	missense	Exon 8 of 15	ENSP00000419975.1	Q8IYB4-1
	PEX5L	ENST00000263962.12	TSL:1	c.742C>G	p.Arg248Gly	missense	Exon 8 of 15	ENSP00000263962.8	Q8IYB4-2
	PEX5L	ENST00000485199.5	TSL:1	c.643C>G	p.Arg215Gly	missense	Exon 7 of 14	ENSP00000418440.1	Q8IYB4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	2.0	M
PhyloP100		6.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.57	N
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.46	T
Polyphen		0.99	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
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs759355045; hg19: chr3-179576924;