NM_153703.5:c.272C>T

Variant names:

• chr1-53070127-C-T
• rs1644095571
• NM_153703.5:c.272C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153703.5(PODN):​c.272C>T​(p.Pro91Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000754 in 1,459,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PODN NM_153703.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• Publications: 0 publications found

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]

ENSG00000232993 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODN	NM_153703.5	MANE Select	c.272C>T	p.Pro91Leu	missense	Exon 2 of 11	NP_714914.3
	PODN	NM_001199080.4		c.272C>T	p.Pro91Leu	missense	Exon 4 of 13	NP_001186009.2	Q7Z5L7-1
	PODN	NM_001199081.3		c.272C>T	p.Pro91Leu	missense	Exon 3 of 12	NP_001186010.2	Q7Z5L7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODN	ENST00000312553.10	TSL:1 MANE Select	c.272C>T	p.Pro91Leu	missense	Exon 2 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.359C>T	p.Pro120Leu	missense	Exon 4 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000395871.7	TSL:5	c.416C>T	p.Pro139Leu	missense	Exon 2 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459374 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 726050

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.82	T
PhyloP100		5.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.63
MVP		0.70
MPC		0.88
ClinPred		1.0	D
GERP RS		4.8
gMVP		0.79
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs1644095571; hg19: chr1-53535799; COSMIC: COSV100439503; COSMIC: COSV100439503;