Variant 19-13933253-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370095.3(PODNL1):c.970G>A(p.Gly324Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,550,738 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

PODNL1
NM_001370095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.18

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018478155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODNL1	NM_001370095.3 linkuse as main transcript	c.970G>A	p.Gly324Arg	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.970G>A	p.Gly324Arg	missense_variant	8/10	3	NM_001370095.3	ENSP00000467395	P1

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000654

AC:

AN:

152946

Hom.:

AF XY:

0.0000596

AC XY:

AN XY:

83900

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000686

AC:

AN:

1398418

Hom.:

Cov.:

AF XY:

0.0000636

AC XY:

AN XY:

691506

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.0000544

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000184

Gnomad4 OTH exome

AF:

0.000600

GnomAD4 genome

AF:

0.000460

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00103

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000526

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Dec 14, 2023

The c.991G>A (p.G331R) alteration is located in exon 8 (coding exon 8) of the PODNL1 gene. This alteration results from a G to A substitution at nucleotide position 991, causing the glycine (G) at amino acid position 331 to be replaced by an arginine (R). 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

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0066

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

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.77

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

M_CAP

Benign

0.074

MetaRNN

Benign

0.018

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.5

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

REVEL

Benign

0.036

Sift

Benign

0.55

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

Sift4G

Benign

0.53

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

Polyphen

0.012

B;.;.;.;B;.;.;.

Vest4

0.14, 0.11, 0.13

MutPred

0.49

Loss of helix (P = 0.028);.;.;.;.;.;.;.;

MVP

0.41

MPC

0.27

ClinPred

0.018

GERP RS

2.5

Varity_R

0.078

gMVP

0.48

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