3-190034157-C-T

Variant names:

• chr3-190034157-C-T
• rs754980
• NM_018192.4:c.481-38715G>A

Variant summary

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

The NM_018192.4(P3H2):​c.481-38715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,932 control chromosomes in the GnomAD database, including 26,923 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 0.57 (26923 hom., cov: 32)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.481-38715G>A		intron_variant	Intron 1 of 14	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.-63-38715G>A		intron_variant	Intron 1 of 14		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332.10	c.481-38715G>A		intron_variant	Intron 1 of 14	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.-63-38715G>A		intron_variant	Intron 1 of 14	1		ENSP00000408947.2
P3H2	ENST00000444866.5	c.-63-38715G>A		intron_variant	Intron 1 of 3	4		ENSP00000391374.1
P3H2	ENST00000426003.1	c.-63-38715G>A		intron_variant	Intron 1 of 3	4		ENSP00000394326.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86325 AN: 151814 Hom.: 26925 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.568 AC: 86337 AN: 151932 Hom.: 26923 Cov.: 32 AF XY: 0.575 AC XY: 42704 AN XY: 74250

African (AFR) AF: 0.282 AC: 11670 AN: 41420

American (AMR) AF: 0.704 AC: 10735 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3295 AN: 5168

South Asian (SAS) AF: 0.706 AC: 3397 AN: 4814

European-Finnish (FIN) AF: 0.732 AC: 7715 AN: 10534

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45290 AN: 67956

Other (OTH) AF: 0.592 AC: 1250 AN: 2110

Alfa AF: 0.623 Hom.: 6385

Bravo AF: 0.552

Asia WGS AF: 0.644 AC: 2232 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.59
PhyloP100		-1.6
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: rs754980; hg19: chr3-189751946;