dbSNP rs201578066: PEX5L:p.Ala254Thr (chr3-179859124-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016559.3(PEX5L):c.760G>A(p.Ala254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

PEX5L
NM_016559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Publications

7 publications found

Variant links:

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]

PEX5L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11615527).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX5L	NM_016559.3	MANE Select	c.760G>A	p.Ala254Thr	missense	Exon 8 of 15	NP_057643.1	Q8IYB4-1
PEX5L	NM_001349386.2		c.925G>A	p.Ala309Thr	missense	Exon 9 of 16	NP_001336315.1
PEX5L	NM_001349387.2		c.832G>A	p.Ala278Thr	missense	Exon 9 of 16	NP_001336316.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX5L	ENST00000467460.6	TSL:1 MANE Select	c.760G>A	p.Ala254Thr	missense	Exon 8 of 15	ENSP00000419975.1	Q8IYB4-1
PEX5L	ENST00000263962.12	TSL:1	c.754G>A	p.Ala252Thr	missense	Exon 8 of 15	ENSP00000263962.8	Q8IYB4-2
PEX5L	ENST00000485199.5	TSL:1	c.655G>A	p.Ala219Thr	missense	Exon 7 of 14	ENSP00000418440.1	Q8IYB4-3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251414

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.000302

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1111792

Other (OTH)

AF:

0.0000331

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000610

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.050

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.0

PhyloP100

1.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.64

REVEL

Benign

0.16

Sift

Benign

0.088

Sift4G

Benign

0.50

Polyphen

0.070

Vest4

0.12

MutPred

0.20

Gain of glycosylation at S253 (P = 0.0151)

MVP

0.51

MPC

0.40

ClinPred

0.047

GERP RS

4.9

Varity_R

0.068

gMVP

0.48

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over