rs837678

chr3-189968092-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• 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/exons	MANE	UniProt
P3H2	NM_018192.4	c.1893+2724C>T		intron_variant		ENST00000319332.10
P3H2	NM_001134418.2	c.1350+2724C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P3H2	ENST00000319332.10	c.1893+2724C>T		intron_variant		1	NM_018192.4	P1
P3H2	ENST00000427335.6	c.1350+2724C>T		intron_variant		1
P3H2	ENST00000463171.5	n.114+2724C>T		intron_variant, non_coding_transcript_variant		5
P3H2	ENST00000467131.1	n.505+2724C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.199

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

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: rs837678; hg19: chr3-189685881;