7-131508980-C-T

Position:

chr7-131508980-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000378555.8(PODXL):c.1072G>A(p.Val358Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,613,412 control chromosomes in the GnomAD database, including 3,201 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.044 ( 258 hom., cov: 31)

Exomes 𝑓: 0.052 ( 2943 hom. )

Consequence

PODXL
ENST00000378555.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.88

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=0.010284156).

BP6

Variant 7-131508980-C-T is Benign according to our data. Variant chr7-131508980-C-T is described in ClinVar as [Benign]. Clinvar id is 1236309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-131508980-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODXL	NM_001018111.3 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant	5/9	ENST00000378555.8	NP_001018121.1
PODXL	NM_005397.4 linkuse as main transcript	c.976G>A	p.Val326Ile	missense_variant	4/8		NP_005388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODXL	ENST00000378555.8 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant	5/9	1	NM_001018111.3	ENSP00000367817	P2	O00592-1
PODXL	ENST00000322985.9 linkuse as main transcript	c.976G>A	p.Val326Ile	missense_variant	4/8	1		ENSP00000319782	A2	O00592-2
PODXL	ENST00000487965.1 linkuse as main transcript	n.423G>A		non_coding_transcript_exon_variant	1/4	2
PODXL	ENST00000446198.5 linkuse as main transcript	c.*337G>A		3_prime_UTR_variant, NMD_transcript_variant	3/7	2		ENSP00000390152

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6752

AN:

152114

Hom.:

258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0463

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0455

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0628

AC:

15795

AN:

251452

Hom.:

913

AF XY:

0.0654

AC XY:

8886

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.0248

Gnomad ASJ exome

AF:

0.0533

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0448

Gnomad NFE exome

AF:

0.0456

Gnomad OTH exome

AF:

0.0550

GnomAD4 exome

AF:

0.0522

AC:

76244

AN:

1461180

Hom.:

2943

Cov.:

AF XY:

0.0540

AC XY:

39256

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.0250

Gnomad4 ASJ exome

AF:

0.0556

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0443

Gnomad4 NFE exome

AF:

0.0445

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0443

AC:

6746

AN:

152232

Hom.:

258

Cov.:

AF XY:

0.0467

AC XY:

3475

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0251

Gnomad4 ASJ

AF:

0.0542

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.0463

Gnomad4 NFE

AF:

0.0455

Gnomad4 OTH

AF:

0.0482

Alfa

AF:

0.0494

Hom.:

599

Bravo

AF:

0.0420

TwinsUK

AF:

0.0453

AC:

168

ALSPAC

AF:

0.0496

AC:

191

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.0472

AC:

406

ExAC

AF:

0.0637

AC:

7729

Asia WGS

AF:

0.130

AC:

452

AN:

3478

EpiCase

AF:

0.0447

EpiControl

AF:

0.0463

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

PODXL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.20

DEOGEN2

Benign

0.083

T;.

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.84

N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.010

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.013

MPC

0.19

ClinPred

0.0012

GERP RS

-7.7

Varity_R

0.017

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