7-131517188-G-C

Variant names:

• chr7-131517188-G-C
• rs11768640
• NM_001018111.3:c.101-5755C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001018111.3(PODXL):​c.101-5755C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PODXL NM_001018111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• atypical juvenile parkinsonism

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PODXL	NM_001018111.3	c.101-5755C>G		intron_variant	Intron 1 of 8	ENST00000378555.8	NP_001018121.1
PODXL	NM_005397.4	c.101-5755C>G		intron_variant	Intron 1 of 7		NP_005388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PODXL	ENST00000378555.8	c.101-5755C>G		intron_variant	Intron 1 of 8	1	NM_001018111.3	ENSP00000367817.3
PODXL	ENST00000322985.9	c.101-5755C>G		intron_variant	Intron 1 of 7	1		ENSP00000319782.9
PODXL	ENST00000446198.5	n.101-5755C>G		intron_variant	Intron 1 of 6	2		ENSP00000390152.1
PODXL	ENST00000465001.1	n.292-5755C>G		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.6
DANN	Benign	0.77
PhyloP100		-0.10

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

Other links and lift over

dbSNP: rs11768640; hg19: chr7-131201947;