rs3735035

Positions:

chr7-131511200-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PODXL	NM_001018111.3 link	c.334G>A	p.Gly112Ser	missense_variant	2/9	ENST00000378555.8	NP_001018121.1	O00592-1Q96N83
PODXL	NM_005397.4 link	c.334G>A	p.Gly112Ser	missense_variant	2/8		NP_005388.2	O00592-2Q96N83

Ensembl

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

GnomAD3 exomes

AF:

0.436

AC:

109490

AN:

251408

Hom.:

25577

AF XY:

0.436

AC XY:

59241

AN XY:

135864

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 SAS exome

AF:

0.358

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

Gnomad4 AFR exome

AF:

0.0796

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.591

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.363

AC:

55032

AN:

151708

Hom.:

12146

Cov.:

AF XY:

0.365

AC XY:

27093

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.0953

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.622

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.498

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.447

Hom.:

39543

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over