NM_153703.5:c.-119C>T

Variant names:

• chr1-53062245-C-T
• rs768589887
• NM_153703.5:c.-119C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153703.5(PODN):​c.-119C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PODN NM_153703.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2787879).

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.-119C>T		5_prime_UTR	Exon 1 of 11	NP_714914.3
	PODN	NM_001199080.4		c.-365C>T		5_prime_UTR	Exon 1 of 13	NP_001186009.2	Q7Z5L7-1
	PODN	NM_001199081.3		c.-175C>T		5_prime_UTR	Exon 1 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.-119C>T		5_prime_UTR	Exon 1 of 11	ENSP00000308315.6	Q7Z5L7-1
	PODN	ENST00000371500.8	TSL:1	c.-278C>T		5_prime_UTR	Exon 1 of 13	ENSP00000360555.3	Q7Z5L7-2
	PODN	ENST00000395871.7	TSL:5	c.26C>T	p.Ala9Val	missense	Exon 1 of 11	ENSP00000379212.3	Q7Z5L7-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152142 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1122918 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 532872

African (AFR) AF: 0.00 AC: 0 AN: 24530

American (AMR) AF: 0.00 AC: 0 AN: 10952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14580

East Asian (EAS) AF: 0.00 AC: 0 AN: 29210

South Asian (SAS) AF: 0.00 AC: 0 AN: 21426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 935908

Other (OTH) AF: 0.00 AC: 0 AN: 44960

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152142 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74294

African (AFR) AF: 0.0000483 AC: 2 AN: 41440

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

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Pathogenic	1.0
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.087
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.040
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.84	P
Vest4		0.24
MutPred		0.35		Gain of sheet (P = 0.0073)
MVP		0.75
MPC		0.36
ClinPred		0.66	D
GERP RS		2.0
PromoterAI		0.013	Neutral
gMVP		0.20
Mutation Taster		=94/6	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: rs768589887; hg19: chr1-53527917;