Genetic Variant PODN:c.-92G>A (chr1-53062272-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153703.5(PODN):c.-92G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000896 in 1,116,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

PODN
NM_153703.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.54

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11439687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153703.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PODN	NM_153703.5	MANE Select	c.-92G>A	5_prime_UTR	Exon 1 of 11	NP_714914.3
PODN	NM_001199080.4		c.-338G>A	5_prime_UTR	Exon 1 of 13	NP_001186009.2	Q7Z5L7-1
PODN	NM_001199081.3		c.-148G>A	5_prime_UTR	Exon 1 of 12	NP_001186010.2	Q7Z5L7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PODN	ENST00000312553.10	TSL:1 MANE Select	c.-92G>A		5_prime_UTR	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1
PODN	ENST00000371500.8	TSL:1	c.-251G>A		5_prime_UTR	Exon 1 of 13	ENSP00000360555.3	Q7Z5L7-2
PODN	ENST00000395871.7	TSL:5	c.53G>A	p.Arg18Gln	missense	Exon 1 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.96e-7

AC:

AN:

1116602

Hom.:

Cov.:

AF XY:

0.00000189

AC XY:

AN XY:

529158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24382

American (AMR)

AF:

0.00

AC:

AN:

10042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14526

East Asian (EAS)

AF:

0.00

AC:

AN:

28840

South Asian (SAS)

AF:

0.00

AC:

AN:

21100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3804

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

932368

Other (OTH)

AF:

0.00

AC:

AN:

44728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.3

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

PhyloP100

-1.5

PROVEAN

Benign

-0.39

REVEL

Benign

0.041

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.28

Vest4

0.069

MutPred

0.42

Loss of methylation at R18 (P = 0.0221)

MVP

0.55

MPC

0.41

ClinPred

0.24

GERP RS

-5.2

PromoterAI

-0.16

Neutral

(source)

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over