3-189957700-AAGAG-A

Position:

• chr3-189957700-AAGAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018192.4(P3H2):​c.*208_*211del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 536,322 control chromosomes in the GnomAD database, including 1,372 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (1226 hom., cov: 0)
  • Exomes 𝑓: 0.034 (146 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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 -10 ACMG points.

• BP6: Variant 3-189957700-AAGAG-A is Benign according to our data. Variant chr3-189957700-AAGAG-A is described in ClinVar as [Benign]. Clinvar id is 1230099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*208_*211del		3_prime_UTR_variant	15/15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*208_*211del		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.*208_*211del		3_prime_UTR_variant	15/15	1	NM_018192.4	ENSP00000316881	P1
P3H2	ENST00000427335.6	c.*208_*211del		3_prime_UTR_variant	15/15	1		ENSP00000408947
P3H2	ENST00000490940.1	n.465_468del		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 12639 AN: 147408 Hom.: 1223 Cov.: 0

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0128

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.00410

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.0293

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0422

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0337 AC: 13098 AN: 388802 Hom.: 146 AF XY: 0.0328 AC XY: 6850 AN XY: 208896

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.00744

Gnomad4 EAS exome AF: 0.0126

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0408

GnomAD4 genome AF: 0.0859 AC: 12678 AN: 147520 Hom.: 1226 Cov.: 0 AF XY: 0.0830 AC XY: 5945 AN XY: 71656

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.00410

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0672

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs3062112; hg19: chr3-189675489;