rs1013368

Variant names:

• chr7-131515880-T-C
• rs1013368
• NM_001018111.3:c.101-4447A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-131515880-T-C
• chr7-131515880-T-G

Variant summary

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

The NM_001018111.3(PODXL):​c.101-4447A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,068 control chromosomes in the GnomAD database, including 9,121 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 0.33 (9121 hom., cov: 32)
• Consequence: PODXL NM_001018111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018111.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODXL	NM_001018111.3	MANE Select	c.101-4447A>G		intron	N/A	NP_001018121.1
	PODXL	NM_005397.4		c.101-4447A>G		intron	N/A	NP_005388.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODXL	ENST00000378555.8	TSL:1 MANE Select	c.101-4447A>G		intron	N/A	ENSP00000367817.3
	PODXL	ENST00000322985.9	TSL:1	c.101-4447A>G		intron	N/A	ENSP00000319782.9
	PODXL	ENST00000923671.1		c.101-4447A>G		intron	N/A	ENSP00000593730.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50822 AN: 151950 Hom.: 9114 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.334 AC: 50852 AN: 152068 Hom.: 9121 Cov.: 32 AF XY: 0.335 AC XY: 24899 AN XY: 74342

African (AFR) AF: 0.220 AC: 9138 AN: 41466

American (AMR) AF: 0.451 AC: 6884 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3472

East Asian (EAS) AF: 0.145 AC: 747 AN: 5166

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4818

European-Finnish (FIN) AF: 0.385 AC: 4076 AN: 10576

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25752 AN: 67988

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.367 Hom.: 17752

Bravo AF: 0.334

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.42
PhyloP100		-0.34
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: rs1013368; hg19: chr7-131200639;