Genetic Variant PODN:c.-119C>G (chr1-53062245-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153703.5(PODN):c.-119C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000863 in 1,275,060 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

PODN
NM_153703.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0870

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20166859).

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.-119C>G	5_prime_UTR	Exon 1 of 11	NP_714914.3
PODN	NM_001199080.4		c.-365C>G	5_prime_UTR	Exon 1 of 13	NP_001186009.2	Q7Z5L7-1
PODN	NM_001199081.3		c.-175C>G	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.-119C>G		5_prime_UTR	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1
PODN	ENST00000371500.8	TSL:1	c.-278C>G		5_prime_UTR	Exon 1 of 13	ENSP00000360555.3	Q7Z5L7-2
PODN	ENST00000395871.7	TSL:5	c.26C>G	p.Ala9Gly	missense	Exon 1 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152142

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:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

56128

AF XY:

0.0000339

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000252

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000712

AC:

AN:

1122918

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

532872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24530

American (AMR)

AF:

0.00

AC:

AN:

10952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14580

East Asian (EAS)

AF:

0.000240

AC:

AN:

29210

South Asian (SAS)

AF:

0.00

AC:

AN:

21426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4054

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

935908

Other (OTH)

AF:

0.00

AC:

AN:

44960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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

AF:

0.0000197

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000967

AC:

Asia WGS

AF:

0.000291

AC:

AN:

3456

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

0.074

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.80

PhyloP100

0.087

PROVEAN

Benign

-0.46

REVEL

Benign

0.037

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.098

Vest4

0.31

MutPred

0.33

Loss of helix (P = 0.0041)

MVP

0.77

MPC

0.37

ClinPred

0.30

GERP RS

2.0

PromoterAI

-0.0060

Neutral

(source)

gMVP

0.13

Mutation Taster

=89/11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over