7-131517188-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018111.3(PODXL):​c.101-5755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,130 control chromosomes in the GnomAD database, including 4,009 homozygotes. 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: 𝑓 0.22 (4009 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PODXL	NM_001018111.3	c.101-5755C>T		intron_variant	Intron 1 of 8	ENST00000378555.8	NP_001018121.1
PODXL	NM_005397.4	c.101-5755C>T		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>T		intron_variant	Intron 1 of 8	1	NM_001018111.3	ENSP00000367817.3
PODXL	ENST00000322985.9	c.101-5755C>T		intron_variant	Intron 1 of 7	1		ENSP00000319782.9
PODXL	ENST00000446198.5	n.101-5755C>T		intron_variant	Intron 1 of 6	2		ENSP00000390152.1
PODXL	ENST00000465001.1	n.292-5755C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33036 AN: 152012 Hom.: 4006 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.217 AC: 33057 AN: 152130 Hom.: 4009 Cov.: 32 AF XY: 0.220 AC XY: 16354 AN XY: 74362

African (AFR) AF: 0.127 AC: 5280 AN: 41494

American (AMR) AF: 0.347 AC: 5299 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3472

East Asian (EAS) AF: 0.140 AC: 727 AN: 5194

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4818

European-Finnish (FIN) AF: 0.238 AC: 2512 AN: 10562

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16293 AN: 67994

Other (OTH) AF: 0.212 AC: 445 AN: 2100

Alfa AF: 0.235 Hom.: 17301

Bravo AF: 0.220

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.8
DANN	Benign	0.87
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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;