1-53069971-G-T

Variant names:

• chr1-53069971-G-T
• rs751610019
• NM_153703.5:c.116G>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.116G>T​(p.Ser39Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S39N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PODN NM_153703.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729
• 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=0.09131062).

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.116G>T	p.Ser39Ile	missense	Exon 2 of 11	NP_714914.3
	PODN	NM_001199080.4		c.116G>T	p.Ser39Ile	missense	Exon 4 of 13	NP_001186009.2	Q7Z5L7-1
	PODN	NM_001199081.3		c.116G>T	p.Ser39Ile	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.116G>T	p.Ser39Ile	missense	Exon 2 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.203G>T	p.Ser68Ile	missense	Exon 4 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000395871.7	TSL:5	c.260G>T	p.Ser87Ile	missense	Exon 2 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000256 AC: 6 AN: 234232 AF XY: 0.0000390

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000285

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1455272 Hom.: 0 Cov.: 35 AF XY: 0.00000691 AC XY: 5 AN XY: 723546

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 43986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39440

South Asian (SAS) AF: 0.00 AC: 0 AN: 85568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109544

Other (OTH) AF: 0.0000167 AC: 1 AN: 60022

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.73
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.079
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.015	D
Polyphen		0.64	P
Vest4		0.42
MutPred		0.32		Loss of phosphorylation at S68 (P = 0.0093)
MVP		0.49
MPC		0.76
ClinPred		0.13	T
GERP RS		3.1
gMVP		0.41
Mutation Taster		=88/12	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: rs751610019; hg19: chr1-53535643;