rs3735035

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018111.3(PODXL):c.334G>A(p.Gly112Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,613,396 control chromosomes in the GnomAD database, including 171,906 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12146 hom., cov: 30)

Exomes 𝑓: 0.46 ( 159760 hom. )

Consequence

PODXL
NM_001018111.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.61

Publications

36 publications found

Variant links:

Genes affected

PODXL (HGNC:9171): (podocalyxin like) This gene encodes a member of the sialomucin protein family. The encoded protein was originally identified as an important component of glomerular podocytes. Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoetic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin. [provided by RefSeq, Jul 2008]

PODXL Gene-Disease associations (from GenCC):

atypical juvenile parkinsonism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PODXL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0459315E-5).

BP6

Variant 7-131511200-C-T is Benign according to our data. Variant chr7-131511200-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PODXL	NM_001018111.3 link	c.334G>A	p.Gly112Ser	missense_variant	Exon 2 of 9	ENST00000378555.8	NP_001018121.1	O00592-1Q96N83
PODXL	NM_005397.4 link	c.334G>A	p.Gly112Ser	missense_variant	Exon 2 of 8		NP_005388.2	O00592-2Q96N83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PODXL	ENST00000378555.8 link	c.334G>A	p.Gly112Ser	missense_variant	Exon 2 of 9	1	NM_001018111.3	ENSP00000367817.3	O00592-1
PODXL	ENST00000322985.9 link	c.334G>A	p.Gly112Ser	missense_variant	Exon 2 of 8	1		ENSP00000319782.9	O00592-2
PODXL	ENST00000446198.5 link	n.334G>A		non_coding_transcript_exon_variant	Exon 2 of 7	2		ENSP00000390152.1	G3V0E6
PODXL	ENST00000465001.1 link	n.525G>A		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55002

AN:

151590

Hom.:

12130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0955

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.436

AC:

109490

AN:

251408

AF XY:

0.436

show subpopulations

Gnomad AFR exome

AF:

0.0877

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

AF:

0.461

AC:

673388

AN:

1461688

Hom.:

159760

Cov.:

AF XY:

0.459

AC XY:

333444

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.0796

AC:

2665

AN:

33478

American (AMR)

AF:

0.425

AC:

18988

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

10344

AN:

26134

East Asian (EAS)

AF:

0.591

AC:

23481

AN:

39700

South Asian (SAS)

AF:

0.356

AC:

30680

AN:

86258

European-Finnish (FIN)

AF:

0.500

AC:

26732

AN:

53414

Middle Eastern (MID)

AF:

0.321

AC:

1854

AN:

5768

European-Non Finnish (NFE)

AF:

0.478

AC:

531842

AN:

1111828

Other (OTH)

AF:

0.444

AC:

26802

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

21774

43549

65323

87098

108872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15612

31224

46836

62448

78060

<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:

0.363

AC:

55032

AN:

151708

Hom.:

12146

Cov.:

AF XY:

0.365

AC XY:

27093

AN XY:

74126

show subpopulations

African (AFR)

AF:

0.0953

AC:

3945

AN:

41398

American (AMR)

AF:

0.380

AC:

5784

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1346

AN:

3468

East Asian (EAS)

AF:

0.622

AC:

3200

AN:

5146

South Asian (SAS)

AF:

0.376

AC:

1794

AN:

4768

European-Finnish (FIN)

AF:

0.498

AC:

5235

AN:

10520

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.478

AC:

32441

AN:

67876

Other (OTH)

AF:

0.375

AC:

787

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1574

3148

4722

6296

7870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.431

Hom.:

49013

Bravo

AF:

0.344

TwinsUK

AF:

0.481

AC:

1783

ALSPAC

AF:

0.470

AC:

1812

ESP6500AA

AF:

0.107

AC:

470

ESP6500EA

AF:

0.473

AC:

4070

ExAC

AF:

0.427

AC:

51851

Asia WGS

AF:

0.505

AC:

1753

AN:

3476

EpiCase

AF:

0.457

EpiControl

AF:

0.445

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.012

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.057

T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.000010

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;N

PhyloP100

-1.6

PrimateAI

Benign

0.22

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.042

Sift

Benign

0.38

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.017

B;B

Vest4

0.053

MPC

0.24

ClinPred

0.0048

GERP RS

-5.6

Varity_R

0.065

gMVP

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over