rs9881766

Positions:

• chr3-189992721-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018192.4(P3H2):​c.823+1373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,028 control chromosomes in the GnomAD database, including 6,987 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 (6987 hom., cov: 32)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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=-0.89).
• 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/exons	MANE	Protein	UniProt
P3H2	NM_018192.4	c.823+1373A>G		intron_variant		ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.280+1373A>G		intron_variant			NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332.10	c.823+1373A>G		intron_variant		1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.280+1373A>G		intron_variant		1		ENSP00000408947.2
P3H2	ENST00000444866.5	c.280+1373A>G		intron_variant		4		ENSP00000391374.1
P3H2	ENST00000426003.1	c.280+1373A>G		intron_variant		4		ENSP00000394326.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44620 AN: 151910 Hom.: 6979 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.294 AC: 44644 AN: 152028 Hom.: 6987 Cov.: 32 AF XY: 0.300 AC XY: 22305 AN XY: 74282

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.270

Alfa AF: 0.318 Hom.: 991

Bravo AF: 0.281

Asia WGS AF: 0.356 AC: 1231 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.75

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: rs9881766; hg19: chr3-189710510;