NM_153703.5:c.149C>T

Variant names:

• chr1-53070004-C-T
• rs759254203
• NM_153703.5:c.149C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153703.5(PODN):​c.149C>T​(p.Pro50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,426 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: 0.000021 (0 hom.)
• Consequence: PODN NM_153703.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.624
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13266659).

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.149C>T	p.Pro50Leu	missense	Exon 2 of 11	NP_714914.3
	PODN	NM_001199080.4		c.149C>T	p.Pro50Leu	missense	Exon 4 of 13	NP_001186009.2	Q7Z5L7-1
	PODN	NM_001199081.3		c.149C>T	p.Pro50Leu	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.149C>T	p.Pro50Leu	missense	Exon 2 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.236C>T	p.Pro79Leu	missense	Exon 4 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000395871.7	TSL:5	c.293C>T	p.Pro98Leu	missense	Exon 2 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

GnomAD2 exomes AF: 0.0000405 AC: 10 AN: 247024 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1460214 Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 10 AN XY: 726442

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.000179 AC: 8 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111778

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000332 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.85	T
PhyloP100		0.62
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.31	B
Vest4		0.42
MVP		0.59
MPC		1.1
ClinPred		0.13	T
GERP RS		4.2
gMVP		0.52
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759254203; hg19: chr1-53535676; COSMIC: COSV57010913; COSMIC: COSV57010913;