Variant 7-131504383-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001018111.3(PODXL):c.1605G>T(p.Gly535=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,162 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 67 hom. )

Consequence

PODXL
NM_001018111.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.407

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 7-131504383-C-A is Benign according to our data. Variant chr7-131504383-C-A is described in ClinVar as [Benign]. Clinvar id is 786111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.407 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PODXL	NM_001018111.3 linkuse as main transcript	c.1605G>T	p.Gly535=	synonymous_variant	9/9	ENST00000378555.8
PODXL	NM_005397.4 linkuse as main transcript	c.1509G>T	p.Gly503=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PODXL	ENST00000378555.8 linkuse as main transcript	c.1605G>T	p.Gly535=	synonymous_variant	9/9	1	NM_001018111.3	P2	O00592-1
PODXL	ENST00000322985.9 linkuse as main transcript	c.1509G>T	p.Gly503=	synonymous_variant	8/8	1		A2	O00592-2
PODXL	ENST00000484346.1 linkuse as main transcript	n.364G>T		non_coding_transcript_exon_variant	2/2	2
PODXL	ENST00000446198.5 linkuse as main transcript	c.*870G>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2455

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0537

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00981

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00467

AC:

1174

AN:

251474

Hom.:

AF XY:

0.00349

AC XY:

474

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0543

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00202

AC:

2947

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1306

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0562

Gnomad4 AMR exome

AF:

0.00555

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000388

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.0161

AC:

2455

AN:

152286

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1165

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0535

Gnomad4 AMR

AF:

0.00973

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.4

DANN

Benign

0.72

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