rs1554391082

Positions:

• chr7-131556270-G-GGGGGCGAC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PP5_Moderate

The NM_001018111.3(PODXL):​c.89_90insGTCGCCCC​(p.Gln32ProfsTer138) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: PODXL NM_001018111.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: -0.516

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.947 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PP5: Variant 7-131556270-G-GGGGGCGAC is Pathogenic according to our data. Variant chr7-131556270-G-GGGGGCGAC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 218942.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODXL	NM_001018111.3	c.89_90insGTCGCCCC	p.Gln32ProfsTer138	frameshift_variant	1/9	ENST00000378555.8	NP_001018121.1
PODXL	NM_005397.4	c.89_90insGTCGCCCC	p.Gln32ProfsTer138	frameshift_variant	1/8		NP_005388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODXL	ENST00000378555.8	c.89_90insGTCGCCCC	p.Gln32ProfsTer138	frameshift_variant	1/9	1	NM_001018111.3	ENSP00000367817	P2
PODXL	ENST00000322985.9	c.89_90insGTCGCCCC	p.Gln32ProfsTer138	frameshift_variant	1/8	1		ENSP00000319782	A2
PODXL	ENST00000446198.5	c.89_90insGTCGCCCC	p.Gln32ProfsTer138	frameshift_variant, NMD_transcript_variant	1/7	2		ENSP00000390152
PODXL	ENST00000465001.1	n.291+854_291+855insGTCGCCCC		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive juvenile Parkinson disease 2 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Prof. Thelma's Laboratory, Department of Genetics, University of Delhi South Campus

Dec 12, 2015

- -

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Mar 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554391082; hg19: chr7-131241029;