Variant rs759639123 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001018111.3(PODXL):c.89_90insGCCGTCGCCGTCGCCGTCGCC(p.Pro24_Pro30dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PODXL
NM_001018111.3 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.516

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PODXL	NM_001018111.3 linkuse as main transcript	c.89_90insGCCGTCGCCGTCGCCGTCGCC	p.Pro24_Pro30dup	inframe_insertion	1/9	ENST00000378555.8
PODXL	NM_005397.4 linkuse as main transcript	c.89_90insGCCGTCGCCGTCGCCGTCGCC	p.Pro24_Pro30dup	inframe_insertion	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PODXL	ENST00000378555.8 linkuse as main transcript	c.89_90insGCCGTCGCCGTCGCCGTCGCC	p.Pro24_Pro30dup	inframe_insertion	1/9	1	NM_001018111.3	P2	O00592-1
PODXL	ENST00000322985.9 linkuse as main transcript	c.89_90insGCCGTCGCCGTCGCCGTCGCC	p.Pro24_Pro30dup	inframe_insertion	1/8	1		A2	O00592-2
PODXL	ENST00000446198.5 linkuse as main transcript	c.89_90insGCCGTCGCCGTCGCCGTCGCC	p.Pro24_Pro30dup	inframe_insertion, NMD_transcript_variant	1/7	2
PODXL	ENST00000465001.1 linkuse as main transcript	n.291+854_291+855insGCCGTCGCCGTCGCCGTCGCC		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000221

AC:

AN:

1311416

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

644804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000259

Gnomad4 OTH exome

AF:

0.0000371

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73860

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jun 01, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with PODXL-related conditions. While this variant is present in population databases (rs759639123), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant, c.69_89dup, results in the insertion of 7 amino acid(s) to the PODXL protein (p.Pro24_Pro30dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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