19-35066536-C-A

Variant names:

• chr19-35066536-C-A
• rs1688029
• NM_001384133.1:c.*249C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384133.1(HPN):​c.*249C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HPN NM_001384133.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

HPN (HGNC:5155): (hepsin) This gene encodes a type II transmembrane serine protease that may be involved in diverse cellular functions, including blood coagulation and the maintenance of cell morphology. Expression of the encoded protein is associated with the growth and progression of cancers, particularly prostate cancer. The protein is cleaved into a catalytic serine protease chain and a non-catalytic scavenger receptor cysteine-rich chain, which associate via a single disulfide bond. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384133.1. 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
	HPN	NM_001384133.1	MANE Select	c.*249C>A		3_prime_UTR	Exon 13 of 13	NP_001371062.1	P05981
	HPN	NM_001375441.3		c.*249C>A		3_prime_UTR	Exon 13 of 13	NP_001362370.1	A0A140VJK9
	HPN	NM_002151.5		c.*249C>A		3_prime_UTR	Exon 14 of 14	NP_002142.1	P05981

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPN	ENST00000672452.2	MANE Select	c.*249C>A		3_prime_UTR	Exon 13 of 13	ENSP00000500664.1	P05981
	HPN	ENST00000262626.6	TSL:1	c.*249C>A		3_prime_UTR	Exon 13 of 13	ENSP00000262626.2	P05981
	HPN	ENST00000392226.5	TSL:1	c.*249C>A		3_prime_UTR	Exon 14 of 14	ENSP00000376060.1	P05981

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 396724 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 205668

African (AFR) AF: 0.00 AC: 0 AN: 11538

American (AMR) AF: 0.00 AC: 0 AN: 15770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12696

East Asian (EAS) AF: 0.00 AC: 0 AN: 29100

South Asian (SAS) AF: 0.00 AC: 0 AN: 32546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 242162

Other (OTH) AF: 0.00 AC: 0 AN: 23562

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1688029;

hg19: chr19-35557440;