NM_018192.4:c.*206_*211dupCTCTCT

Variant names:

• chr3-189957698-AGA-AGAAGAG
• rs3062112
• NM_018192.4:c.*208_*211dupCTCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018192.4(P3H2):​c.*208_*211dupCTCT 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 0.020 (55 hom., cov: 0)
  • Exomes 𝑓: 0.0073 (6 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

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]

P3H2 Gene-Disease associations (from GenCC):

• myopia, high, with cataract and vitreoretinal degeneration

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-189957698-AGA-AGAAGAG is Benign according to our data. Variant chr3-189957700-A-AAGAG is described in ClinVar as Benign. ClinVar VariationId is 1277801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	NM_018192.4	MANE Select	c.*208_*211dupCTCT		3_prime_UTR	Exon 15 of 15	NP_060662.2
	P3H2	NM_001134418.2		c.*208_*211dupCTCT		3_prime_UTR	Exon 15 of 15	NP_001127890.1	Q8IVL5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	ENST00000319332.10	TSL:1 MANE Select	c.*208_*211dupCTCT		3_prime_UTR	Exon 15 of 15	ENSP00000316881.5	Q8IVL5-1
	P3H2	ENST00000427335.6	TSL:1	c.*208_*211dupCTCT		3_prime_UTR	Exon 15 of 15	ENSP00000408947.2	Q8IVL5-2
	P3H2	ENST00000895815.1		c.*208_*211dupCTCT		3_prime_UTR	Exon 15 of 15	ENSP00000565874.1

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2896 AN: 147444 Hom.: 55 Cov.: 0

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.000879

Gnomad EAS AF: 0.00624

Gnomad SAS AF: 0.00220

Gnomad FIN AF: 0.00308

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00727 AC: 2856 AN: 392910 Hom.: 6 Cov.: 0 AF XY: 0.00682 AC XY: 1439 AN XY: 211052

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0557 AC: 624 AN: 11198

American (AMR) AF: 0.00793 AC: 134 AN: 16908

Ashkenazi Jewish (ASJ) AF: 0.00248 AC: 29 AN: 11690

East Asian (EAS) AF: 0.00582 AC: 151 AN: 25958

South Asian (SAS) AF: 0.00336 AC: 145 AN: 43118

European-Finnish (FIN) AF: 0.00745 AC: 172 AN: 23098

Middle Eastern (MID) AF: 0.00657 AC: 11 AN: 1674

European-Non Finnish (NFE) AF: 0.00572 AC: 1355 AN: 237004

Other (OTH) AF: 0.0106 AC: 235 AN: 22262

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0197 AC: 2902 AN: 147554 Hom.: 55 Cov.: 0 AF XY: 0.0192 AC XY: 1379 AN XY: 71672

African (AFR) AF: 0.0606 AC: 2431 AN: 40134

American (AMR) AF: 0.0112 AC: 166 AN: 14758

Ashkenazi Jewish (ASJ) AF: 0.000879 AC: 3 AN: 3414

East Asian (EAS) AF: 0.00625 AC: 31 AN: 4958

South Asian (SAS) AF: 0.00243 AC: 11 AN: 4536

European-Finnish (FIN) AF: 0.00308 AC: 30 AN: 9754

Middle Eastern (MID) AF: 0.00699 AC: 2 AN: 286

European-Non Finnish (NFE) AF: 0.00301 AC: 201 AN: 66814

Other (OTH) AF: 0.0132 AC: 27 AN: 2040

Alfa AF: 0.000477 Hom.: 390

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3062112; hg19: chr3-189675487;