3-189957700-AAGAGAGAGAG-AAGAGAGAGAGAG

Variant names:

• chr3-189957700-A-AAG
• rs3062112
• ENST00000319332:c.*210_*211dupCT

Variant summary

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

The NM_018192.4(P3H2):​c.*210_*211dupCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (1040 hom., cov: 0)
  • Exomes 𝑓: 0.033 (45 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-A-AAG is Benign according to our data. Variant chr3-189957700-A-AAG is described in ClinVar as [Benign]. Clinvar id is 1280894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*210_*211dupCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*210_*211dupCT		3_prime_UTR_variant	Exon 15 of 15		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332	c.*210_*211dupCT		3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335	c.*210_*211dupCT		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2
P3H2	ENST00000490940.1	n.467_468dupCT		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 10943 AN: 147398 Hom.: 1041 Cov.: 0

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0111

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.000716

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.00515

Gnomad OTH AF: 0.0530

GnomAD4 exome AF: 0.0335 AC: 13203 AN: 394628 Hom.: 45 Cov.: 0 AF XY: 0.0327 AC XY: 6928 AN XY: 212060

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0629

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.0401

Gnomad4 FIN exome AF: 0.00300

Gnomad4 NFE exome AF: 0.00567

Gnomad4 OTH exome AF: 0.0382

GnomAD4 genome AF: 0.0743 AC: 10965 AN: 147508 Hom.: 1040 Cov.: 0 AF XY: 0.0752 AC XY: 5386 AN XY: 71662

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0111

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.0455

Gnomad4 FIN AF: 0.000716

Gnomad4 NFE AF: 0.00513

Gnomad4 OTH AF: 0.0529

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 26, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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;