dbSNP rs4731799: PODXL:c.101-1983C>T (chr7-131513416-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001018111.3(PODXL):c.101-1983C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,098 control chromosomes in the GnomAD database, including 11,719 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 0.36 ( 11719 hom., cov: 32)

Consequence

PODXL
NM_001018111.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

Publications

2 publications found

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 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

PODXL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PODXL	NM_001018111.3 link	c.101-1983C>T		intron_variant	Intron 1 of 8	ENST00000378555.8	NP_001018121.1	O00592-1Q96N83
PODXL	NM_005397.4 link	c.101-1983C>T		intron_variant	Intron 1 of 7		NP_005388.2	O00592-2Q96N83

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PODXL	ENST00000378555.8 link	c.101-1983C>T	intron_variant	Intron 1 of 8	1	NM_001018111.3	ENSP00000367817.3	O00592-1
PODXL	ENST00000322985.9 link	c.101-1983C>T	intron_variant	Intron 1 of 7	1		ENSP00000319782.9	O00592-2
PODXL	ENST00000446198.5 link	n.101-1983C>T	intron_variant	Intron 1 of 6	2		ENSP00000390152.1	G3V0E6
PODXL	ENST00000465001.1 link	n.292-1983C>T	intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54038

AN:

151978

Hom.:

11702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0953

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.363

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

GnomAD4 genome

AF:

0.356

AC:

54071

AN:

152098

Hom.:

11719

Cov.:

AF XY:

0.359

AC XY:

26711

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0952

AC:

3954

AN:

41532

American (AMR)

AF:

0.364

AC:

5562

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1314

AN:

3472

East Asian (EAS)

AF:

0.625

AC:

3228

AN:

5162

South Asian (SAS)

AF:

0.377

AC:

1812

AN:

4802

European-Finnish (FIN)

AF:

0.492

AC:

5209

AN:

10582

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31707

AN:

67956

Other (OTH)

AF:

0.371

AC:

783

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1596

3192

4789

6385

7981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.419

Hom.:

38913

Bravo

AF:

0.337

Asia WGS

AF:

0.510

AC:

1772

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.5

(source)

DANN

Benign

0.65

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over