3-189963769-C-T

Variant names:

• chr3-189963769-C-T
• rs1719581
• NM_018192.4:c.2034+189G>A

Variant summary

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

The NM_018192.4(P3H2):​c.2034+189G>A variant causes a intron 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 1 publications found

Genes affected

P3H2 (HGNC:19317): (prolyl 3-hydroxylase 2) This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

P3H2 Gene-Disease associations (from GenCC):

• myopia, high, with cataract and vitreoretinal degeneration

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P

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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018192.4. 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
	P3H2	NM_018192.4	MANE Select	c.2034+189G>A		intron	N/A	NP_060662.2
	P3H2	NM_001134418.2		c.1491+189G>A		intron	N/A	NP_001127890.1	Q8IVL5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	ENST00000319332.10	TSL:1 MANE Select	c.2034+189G>A		intron	N/A	ENSP00000316881.5	Q8IVL5-1
	P3H2	ENST00000427335.6	TSL:1	c.1491+189G>A		intron	N/A	ENSP00000408947.2	Q8IVL5-2
	P3H2	ENST00000895815.1		c.2103+189G>A		intron	N/A	ENSP00000565874.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 511886 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 272280

African (AFR) AF: 0.00 AC: 0 AN: 14544

American (AMR) AF: 0.00 AC: 0 AN: 27490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15254

East Asian (EAS) AF: 0.00 AC: 0 AN: 31758

South Asian (SAS) AF: 0.00 AC: 0 AN: 52916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2086

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 309342

Other (OTH) AF: 0.00 AC: 0 AN: 28152

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.66
PhyloP100		-1.4

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: rs1719581; hg19: chr3-189681558;