rs1719596

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P3H2	NM_018192.4	c.633+338T>C		intron_variant		ENST00000319332.10
P3H2	NM_001134418.2	c.90+338T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P3H2	ENST00000319332.10	c.633+338T>C		intron_variant		1	NM_018192.4	P1
P3H2	ENST00000427335.6	c.90+338T>C		intron_variant		1
P3H2	ENST00000426003.1	c.90+338T>C		intron_variant		4
P3H2	ENST00000444866.5	c.90+338T>C		intron_variant		4

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

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.888

Alfa AF: 0.905 Hom.: 33701

Bravo AF: 0.922

Asia WGS AF: 0.854 AC: 2970 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1719596; hg19: chr3-189712741;