Variant chr1-53070090-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153703.5(PODN):c.235G>A(p.Val79Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,612,946 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

PODN
NM_153703.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Variant links:

Genes affected

PODN (HGNC:23174): (podocan) The protein encoded by this gene is a member of the small leucine-rich repeat protein family and contains an amino terminal CX3CXCX7C cysteine-rich cluster followed by a leucine-rich repeat domain. Studies suggest that this protein could function to inhibit smooth muscle cell proliferation and migration following arterial injury. [provided by RefSeq, Jul 2016]

PODN links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025538683).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PODN	NM_153703.5 linkuse as main transcript	c.235G>A	p.Val79Ile	missense_variant	2/11	ENST00000312553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PODN	ENST00000312553.10 linkuse as main transcript	c.235G>A	p.Val79Ile	missense_variant	2/11	1	NM_153703.5	A2	Q7Z5L7-1
	ENST00000447867.1 linkuse as main transcript	n.369-54C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000656

AC:

164

AN:

250056

Hom.:

AF XY:

0.000774

AC XY:

105

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000762

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000518

AC:

756

AN:

1460602

Hom.:

Cov.:

AF XY:

0.000588

AC XY:

427

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000391

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000558

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000680

Hom.:

Bravo

AF:

0.000620

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000709

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00142

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2022

The c.379G>A (p.V127I) alteration is located in exon 2 (coding exon 2) of the PODN gene. This alteration results from a G to A substitution at nucleotide position 379, causing the valine (V) at amino acid position 127 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

-0.060

Eigen_PC

Benign

-0.013

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.52

T;.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.24

N;N;.;N

REVEL

Benign

0.10

Sift

Benign

0.32

T;T;.;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.076

B;D;D;P

Vest4

0.41

MVP

0.49

MPC

0.32

ClinPred

0.016

GERP RS

4.7

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over