3-189997806-T-C

Variant names:

• chr3-189997806-T-C
• rs981890
• NM_018192.4:c.481-2364A>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.481-2364A>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 152,074 control chromosomes in the GnomAD database, including 6,849 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 (6849 hom., cov: 33)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• 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: G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.481-2364A>G		intron_variant	Intron 1 of 14	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.-63-2364A>G		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.481-2364A>G		intron_variant	Intron 1 of 14	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.-63-2364A>G		intron_variant	Intron 1 of 14	1		ENSP00000408947.2
P3H2	ENST00000444866.5	c.-63-2364A>G		intron_variant	Intron 1 of 3	4		ENSP00000391374.1
P3H2	ENST00000426003.1	c.-63-2364A>G		intron_variant	Intron 1 of 3	4		ENSP00000394326.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44374 AN: 151956 Hom.: 6840 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.292 AC: 44399 AN: 152074 Hom.: 6849 Cov.: 33 AF XY: 0.297 AC XY: 22065 AN XY: 74332

African (AFR) AF: 0.210 AC: 8711 AN: 41492

American (AMR) AF: 0.304 AC: 4644 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2512 AN: 5180

South Asian (SAS) AF: 0.326 AC: 1572 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4379 AN: 10540

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

European-Non Finnish (NFE) AF: 0.309 AC: 21037 AN: 67978

Other (OTH) AF: 0.263 AC: 555 AN: 2108

Alfa AF: 0.308 Hom.: 972

Bravo AF: 0.281

Asia WGS AF: 0.347 AC: 1206 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.8
DANN	Benign	0.73
PhyloP100		0.77
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: rs981890; hg19: chr3-189715595;