rs761072151

Variant names:

• chr1-53062290-C-T
• rs761072151
• NM_153703.5:c.-74C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153703.5(PODN):​c.-74C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 1,259,948 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 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: PODN NM_153703.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.181
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068618357).

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.-74C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_714914.3
	PODN	NM_153703.5	MANE Select	c.-74C>T		5_prime_UTR	Exon 1 of 11	NP_714914.3
	PODN	NM_001199080.4		c.-320C>T		5_prime_UTR_premature_start_codon_gain	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.-74C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.-233C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000312553.10	TSL:1 MANE Select	c.-74C>T		5_prime_UTR	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152118 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000630 AC: 2 AN: 31756 AF XY: 0.0000606

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000670

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000451 AC: 5 AN: 1107830 Hom.: 0 Cov.: 32 AF XY: 0.00000381 AC XY: 2 AN XY: 524256

African (AFR) AF: 0.00 AC: 0 AN: 23982

American (AMR) AF: 0.000441 AC: 4 AN: 9070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14454

East Asian (EAS) AF: 0.00 AC: 0 AN: 28166

South Asian (SAS) AF: 0.00 AC: 0 AN: 20564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3504

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 927496

Other (OTH) AF: 0.00 AC: 0 AN: 44340

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152118 Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.000327 AC: 5 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000166

ExAC AF: 0.000135 AC: 12

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	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.18
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.038
Sift	Benign	0.041	D
Sift4G	Uncertain	0.025	D
Polyphen		0.028	B
Vest4		0.097
MutPred		0.19		Loss of phosphorylation at S24 (P = 0.0026)
MVP		0.39
MPC		0.32
ClinPred		0.070	T
GERP RS		1.2
PromoterAI		-0.16	Neutral
gMVP		0.18
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: rs761072151; hg19: chr1-53527962;