chr3-189957778-C-T

Position:

• chr3-189957778-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018192.4(P3H2):​c.*134G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 687,132 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (15 hom., cov: 31)
  • Exomes 𝑓: 0.016 (100 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.666

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 3-189957778-C-T is Benign according to our data. Variant chr3-189957778-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0112 (1701/151920) while in subpopulation SAS AF= 0.0244 (117/4804). AF 95% confidence interval is 0.0208. There are 15 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*134G>A		3_prime_UTR_variant	15/15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*134G>A		3_prime_UTR_variant	15/15		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332.10	c.*134G>A		3_prime_UTR_variant	15/15	1	NM_018192.4	ENSP00000316881	P1
P3H2	ENST00000427335.6	c.*134G>A		3_prime_UTR_variant	15/15	1		ENSP00000408947
P3H2	ENST00000490940.1	n.391G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1702 AN: 151800 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00561

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0156 AC: 8334 AN: 535212 Hom.: 100 Cov.: 6 AF XY: 0.0165 AC XY: 4739 AN XY: 287776

Gnomad4 AFR exome AF: 0.00366

Gnomad4 AMR exome AF: 0.00955

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.0000631

Gnomad4 SAS exome AF: 0.0252

Gnomad4 FIN exome AF: 0.00621

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0112 AC: 1701 AN: 151920 Hom.: 15 Cov.: 31 AF XY: 0.0108 AC XY: 802 AN XY: 74242

Gnomad4 AFR AF: 0.00285

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.00561

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0152 Hom.: 4

Bravo AF: 0.0111

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.7
DANN	Benign	0.81

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: rs145678898; hg19: chr3-189675567;