1-53062248-A-G

Position:

• chr1-53062248-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153703.5(PODN):​c.-116A>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 0.00000623 in 1,123,084 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PODN NM_153703.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.108

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17030343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PODN	NM_153703.5	c.-116A>G		5_prime_UTR_variant	1/11	ENST00000312553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PODN	ENST00000312553.10	c.-116A>G		5_prime_UTR_variant	1/11	1	NM_153703.5	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000623 AC: 7 AN: 1123084 Hom.: 0 Cov.: 30 AF XY: 0.00000938 AC XY: 5 AN XY: 532960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000534

Gnomad4 OTH exome AF: 0.0000222

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000375 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.29A>G (p.Q10R) alteration is located in exon 1 (coding exon 1) of the PODN gene. This alteration results from a A to G substitution at nucleotide position 29, causing the glutamine (Q) at amino acid position 10 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.98
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.41	T;T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D;N;N
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.039
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.12	B;B
Vest4		0.14
MVP		0.69
MPC		0.38
ClinPred		0.27	T
GERP RS		0.057
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs1643966723; hg19: chr1-53527920;