NM_018192.4:c.481-59786G>A

Variant names:

• chr3-190055228-C-T
• rs7627711
• NM_018192.4:c.481-59786G>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.481-59786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,992 control chromosomes in the GnomAD database, including 13,299 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 0.40 (13299 hom., cov: 32)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.481-59786G>A		intron_variant	Intron 1 of 14	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.-63-59786G>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.481-59786G>A		intron_variant	Intron 1 of 14	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.-63-59786G>A		intron_variant	Intron 1 of 14	1		ENSP00000408947.2
P3H2	ENST00000444866.5	c.-63-59786G>A		intron_variant	Intron 1 of 3	4		ENSP00000391374.1
P3H2	ENST00000426003.1	c.-63-59786G>A		intron_variant	Intron 1 of 3	4		ENSP00000394326.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60666 AN: 151874 Hom.: 13258 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.400 AC: 60767 AN: 151992 Hom.: 13299 Cov.: 32 AF XY: 0.396 AC XY: 29442 AN XY: 74284

African (AFR) AF: 0.604 AC: 25043 AN: 41438

American (AMR) AF: 0.280 AC: 4274 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1536 AN: 5150

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4820

European-Finnish (FIN) AF: 0.294 AC: 3110 AN: 10576

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22887 AN: 67952

Other (OTH) AF: 0.385 AC: 814 AN: 2114

Alfa AF: 0.346 Hom.: 6954

Bravo AF: 0.409

Asia WGS AF: 0.310 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.051
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: rs7627711; hg19: chr3-189773017;