1-53062306-C-G

Variant names:

• chr1-53062306-C-G
• rs762570759
• NM_153703.5:c.-58C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153703.5(PODN):​c.-58C>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,253,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PODN NM_153703.5 splice_region
• Scores: Splicing: ADA: 0.04671
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23196223).

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.-58C>G		splice_region	Exon 1 of 11	NP_714914.3
	PODN	NM_153703.5	MANE Select	c.-58C>G		5_prime_UTR	Exon 1 of 11	NP_714914.3
	PODN	NM_001199080.4		c.-304C>G		splice_region	Exon 1 of 13	NP_001186009.2	Q7Z5L7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODN	ENST00000312553.10	TSL:1 MANE Select	c.-58C>G		splice_region	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.-217C>G		splice_region	Exon 1 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000312553.10	TSL:1 MANE Select	c.-58C>G		5_prime_UTR	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152096 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000876 AC: 2 AN: 22834 AF XY: 0.0000849

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000173 AC: 190 AN: 1101110 Hom.: 0 Cov.: 32 AF XY: 0.000181 AC XY: 94 AN XY: 520692

African (AFR) AF: 0.0000425 AC: 1 AN: 23518

American (AMR) AF: 0.00 AC: 0 AN: 8606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14392

East Asian (EAS) AF: 0.00 AC: 0 AN: 27566

South Asian (SAS) AF: 0.00 AC: 0 AN: 20100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3306

European-Non Finnish (NFE) AF: 0.000199 AC: 184 AN: 923768

Other (OTH) AF: 0.000114 AC: 5 AN: 44034

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152096 Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67998

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000526 AC: 4

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	0.20
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.93
Eigen	Benign	0.10
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.8
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.058
Sift	Uncertain	0.010	D
Sift4G	Benign	0.086	T
Polyphen		0.90	P
Vest4		0.20
MutPred		0.20		Loss of phosphorylation at S29 (P = 0.0031)
MVP		0.73
MPC		0.40
ClinPred		0.13	T
GERP RS		2.2
PromoterAI		-0.21	Neutral
gMVP		0.20
Mutation Taster		=292/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.047
dbscSNV1_RF	Benign	0.20
SpliceAI score (max)		0.020		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: rs762570759; hg19: chr1-53527978;