1-53069976-G-C

Variant names:

• chr1-53069976-G-C
• rs113957899
• NM_153703.5:c.121G>C

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.121G>C​(p.Glu41Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PODN NM_153703.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• Publications: 1 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=0.16014847).

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.121G>C	p.Glu41Gln	missense	Exon 2 of 11	NP_714914.3
	PODN	NM_001199080.4		c.121G>C	p.Glu41Gln	missense	Exon 4 of 13	NP_001186009.2	Q7Z5L7-1
	PODN	NM_001199081.3		c.121G>C	p.Glu41Gln	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.121G>C	p.Glu41Gln	missense	Exon 2 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.208G>C	p.Glu70Gln	missense	Exon 4 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000395871.7	TSL:5	c.265G>C	p.Glu89Gln	missense	Exon 2 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.10
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.85	T
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.078
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.084	T
Polyphen		0.048	B
Vest4		0.40
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0507)
MVP		0.78
MPC		0.70
ClinPred		0.85	D
GERP RS		4.0
gMVP		0.45
Mutation Taster		=96/4	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: rs113957899; hg19: chr1-53535648;