rs837678

Variant names:

• chr3-189968092-G-A
• rs837678
• NM_018192.4:c.1893+2724C>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.1893+2724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,048 control chromosomes in the GnomAD database, including 3,444 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 0.20 (3444 hom., cov: 31)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.1893+2724C>T		intron_variant	Intron 13 of 14	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.1350+2724C>T		intron_variant	Intron 13 of 14		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332.10	c.1893+2724C>T		intron_variant	Intron 13 of 14	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.1350+2724C>T		intron_variant	Intron 13 of 14	1		ENSP00000408947.2
P3H2	ENST00000463171.5	n.114+2724C>T		intron_variant	Intron 2 of 2	5
P3H2	ENST00000467131.1	n.505+2724C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29705 AN: 151930 Hom.: 3441 Cov.: 31

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.195 AC: 29715 AN: 152048 Hom.: 3444 Cov.: 31 AF XY: 0.192 AC XY: 14294 AN XY: 74312

African (AFR) AF: 0.0698 AC: 2898 AN: 41494

American (AMR) AF: 0.168 AC: 2565 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3466

East Asian (EAS) AF: 0.189 AC: 976 AN: 5164

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4818

European-Finnish (FIN) AF: 0.224 AC: 2358 AN: 10548

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18346 AN: 67960

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.237 Hom.: 928

Bravo AF: 0.184

Asia WGS AF: 0.178 AC: 622 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.24
PhyloP100		-0.68
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: rs837678; hg19: chr3-189685881;