Genetic Variant NM_001018111.3:c.1214G>C (chr7-131506614-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001018111.3(PODXL):c.1214G>C(p.Ser405Thr) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S405N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PODXL
NM_001018111.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Publications

0 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:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.0609186).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODXL	NM_001018111.3	MANE Select	c.1214G>C	p.Ser405Thr	missense	Exon 6 of 9	NP_001018121.1
	PODXL	NM_005397.4		c.1118G>C	p.Ser373Thr	missense	Exon 5 of 8	NP_005388.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PODXL	ENST00000378555.8	TSL:1 MANE Select	c.1214G>C	p.Ser405Thr	missense	Exon 6 of 9	ENSP00000367817.3
PODXL	ENST00000322985.9	TSL:1	c.1118G>C	p.Ser373Thr	missense	Exon 5 of 8	ENSP00000319782.9
PODXL	ENST00000446198.5	TSL:2	n.*479G>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000390152.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.035

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.14

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.22

M_CAP

Benign

0.0099

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-2.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

REVEL

Benign

0.013

Sift

Benign

0.049

Sift4G

Benign

0.39

Polyphen

0.14

Vest4

0.062

MutPred

0.43

Gain of phosphorylation at S405 (P = 0.1778)

MVP

0.099

MPC

0.47

ClinPred

0.14

GERP RS

-3.8

Varity_R

0.098

gMVP

0.27

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over