3-189993000-T-C

Variant names:

• chr3-189993000-T-C
• rs9882242
• NM_018192.4:c.823+1094A>G

Variant summary

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

The NM_018192.4(P3H2):​c.823+1094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,094 control chromosomes in the GnomAD database, including 6,956 homozygotes. 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 0.29 (6956 hom., cov: 32)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 0 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

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.823+1094A>G		intron	N/A	NP_060662.2
	P3H2	NM_001134418.2		c.280+1094A>G		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.823+1094A>G		intron	N/A	ENSP00000316881.5	Q8IVL5-1
	P3H2	ENST00000427335.6	TSL:1	c.280+1094A>G		intron	N/A	ENSP00000408947.2	Q8IVL5-2
	P3H2	ENST00000895815.1		c.823+1094A>G		intron	N/A	ENSP00000565874.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44324 AN: 151976 Hom.: 6948 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44340 AN: 152094 Hom.: 6956 Cov.: 32 AF XY: 0.298 AC XY: 22173 AN XY: 74342

African (AFR) AF: 0.185 AC: 7690 AN: 41510

American (AMR) AF: 0.307 AC: 4686 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2506 AN: 5164

South Asian (SAS) AF: 0.352 AC: 1697 AN: 4818

European-Finnish (FIN) AF: 0.427 AC: 4505 AN: 10560

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21656 AN: 67984

Other (OTH) AF: 0.269 AC: 568 AN: 2112

Alfa AF: 0.305 Hom.: 1115

Bravo AF: 0.278

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.3
DANN	Benign	0.46
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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: rs9882242; hg19: chr3-189710789;