rs1719596

Variant names:

• chr3-189994952-A-G
• rs1719596
• NM_018192.4:c.633+338T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-189994952-A-G
• chr3-189994952-A-T

Variant summary

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

The NM_018192.4(P3H2):​c.633+338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,032 control chromosomes in the GnomAD database, including 64,666 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 0.92 (64666 hom., cov: 30)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• 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: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	NM_018192.4	MANE Select	c.633+338T>C		intron	N/A	NP_060662.2
	P3H2	NM_001134418.2		c.90+338T>C		intron	N/A	NP_001127890.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	ENST00000319332.10	TSL:1 MANE Select	c.633+338T>C		intron	N/A	ENSP00000316881.5
	P3H2	ENST00000427335.6	TSL:1	c.90+338T>C		intron	N/A	ENSP00000408947.2
	P3H2	ENST00000444866.5	TSL:4	c.90+338T>C		intron	N/A	ENSP00000391374.1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 139958 AN: 151914 Hom.: 64600 Cov.: 30

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.921 AC: 140082 AN: 152032 Hom.: 64666 Cov.: 30 AF XY: 0.921 AC XY: 68423 AN XY: 74318

African (AFR) AF: 0.979 AC: 40656 AN: 41528

American (AMR) AF: 0.905 AC: 13821 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2826 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4854 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4050 AN: 4814

European-Finnish (FIN) AF: 0.914 AC: 9590 AN: 10496

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61440 AN: 67968

Other (OTH) AF: 0.888 AC: 1871 AN: 2108

Alfa AF: 0.907 Hom.: 47645

Bravo AF: 0.922

Asia WGS AF: 0.854 AC: 2970 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.68
PhyloP100		-0.26
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: rs1719596; hg19: chr3-189712741;