1-53084515-C-T

Variant names:

• chr1-53084515-C-T
• rs899974
• NM_153703.5:c.*30C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153703.5(PODN):​c.*30C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,144 control chromosomes in the GnomAD database, including 57,869 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.87 (57744 hom., cov: 29)
  • Exomes 𝑓: 0.96 (125 hom.)
• Consequence: PODN NM_153703.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODN	NM_153703.5	MANE Select	c.*30C>T		splice_region	Exon 11 of 11	NP_714914.3
	PODN	NM_153703.5	MANE Select	c.*30C>T		3_prime_UTR	Exon 11 of 11	NP_714914.3
	PODN	NM_001199080.4		c.*30C>T		splice_region	Exon 13 of 13	NP_001186009.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODN	ENST00000312553.10	TSL:1 MANE Select	c.*30C>T		splice_region	Exon 11 of 11	ENSP00000308315.6
	PODN	ENST00000371500.8	TSL:1	c.*30C>T		splice_region	Exon 13 of 13	ENSP00000360555.3
	PODN	ENST00000312553.10	TSL:1 MANE Select	c.*30C>T		3_prime_UTR	Exon 11 of 11	ENSP00000308315.6

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131394 AN: 151752 Hom.: 57720 Cov.: 29

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.890

GnomAD4 exome AF: 0.956 AC: 262 AN: 274 Hom.: 125 Cov.: 0 AF XY: 0.953 AC XY: 183 AN XY: 192

African (AFR) AF: 0.900 AC: 9 AN: 10

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.917 AC: 22 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.963 AC: 210 AN: 218

Other (OTH) AF: 1.00 AC: 14 AN: 14

GnomAD4 genome AF: 0.866 AC: 131466 AN: 151870 Hom.: 57744 Cov.: 29 AF XY: 0.863 AC XY: 64049 AN XY: 74220

African (AFR) AF: 0.754 AC: 31181 AN: 41372

American (AMR) AF: 0.741 AC: 11319 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3368 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3799 AN: 5122

South Asian (SAS) AF: 0.903 AC: 4333 AN: 4800

European-Finnish (FIN) AF: 0.953 AC: 10112 AN: 10610

Middle Eastern (MID) AF: 0.966 AC: 282 AN: 292

European-Non Finnish (NFE) AF: 0.947 AC: 64334 AN: 67912

Other (OTH) AF: 0.886 AC: 1870 AN: 2110

Alfa AF: 0.914 Hom.: 118341

Bravo AF: 0.843

Asia WGS AF: 0.785 AC: 2730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.74
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs899974; hg19: chr1-53550187;