Variant 19-13932834-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001370095.3(PODNL1):c.1389C>G(p.Ile463Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,612,708 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 3 hom. )

Consequence

PODNL1
NM_001370095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.321

Variant links:

Genes affected

PODNL1 (HGNC:26275): (podocan like 1) Predicted to be located in collagen-containing extracellular matrix. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

PODNL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14898783).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODNL1	NM_001370095.3 linkuse as main transcript	c.1389C>G	p.Ile463Met	missense_variant	8/10	ENST00000588872.3	NP_001357024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODNL1	ENST00000588872.3 linkuse as main transcript	c.1389C>G	p.Ile463Met	missense_variant	8/10	3	NM_001370095.3	ENSP00000467395	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000102

AC:

AN:

245924

Hom.:

AF XY:

0.000171

AC XY:

AN XY:

134314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000785

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1460358

Hom.:

Cov.:

AF XY:

0.0000964

AC XY:

AN XY:

726488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000826

AC:

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

Sep 01, 2021

The c.1410C>G (p.I470M) alteration is located in exon 8 (coding exon 8) of the PODNL1 gene. This alteration results from a C to G substitution at nucleotide position 1410, causing the isoleucine (I) at amino acid position 470 to be replaced by a methionine (M). 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

-0.35

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0080

.;T;.;.;.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.83

T;T;T;T;T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.15

T;T;T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.7

.;M;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

.;.;.;N;.;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0060

.;.;.;D;.;D;D

Sift4G

Uncertain

0.030

D;.;.;D;.;T;T

Polyphen

0.95, 1.0

.;P;.;.;.;D;.

Vest4

0.39, 0.44, 0.43

MutPred

0.42

.;Gain of solvent accessibility (P = 0.0086);.;.;.;.;.;

MVP

0.70

MPC

0.83

ClinPred

0.23

GERP RS

-1.6

Varity_R

0.17

gMVP

0.64

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