3-189957700-AAGAGAGAGAG-AAG

Variant names:

• chr3-189957700-AAGAGAGAG-A
• rs3062112
• NM_018192.4:c.*204_*211delCTCTCTCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018192.4(P3H2):​c.*204_*211delCTCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 543,352 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 0)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00461 (681/147612) while in subpopulation AFR AF = 0.0158 (633/40152). AF 95% confidence interval is 0.0147. There are 3 homozygotes in GnomAd4. There are 303 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.*204_*211delCTCTCTCT		3_prime_UTR	Exon 15 of 15	NP_060662.2
	P3H2	NM_001134418.2		c.*204_*211delCTCTCTCT		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.*204_*211delCTCTCTCT		3_prime_UTR	Exon 15 of 15	ENSP00000316881.5	Q8IVL5-1
	P3H2	ENST00000427335.6	TSL:1	c.*204_*211delCTCTCTCT		3_prime_UTR	Exon 15 of 15	ENSP00000408947.2	Q8IVL5-2
	P3H2	ENST00000895815.1		c.*204_*211delCTCTCTCT		3_prime_UTR	Exon 15 of 15	ENSP00000565874.1

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 681 AN: 147502 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00224

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000898

Gnomad OTH AF: 0.00446

GnomAD4 exome AF: 0.000576 AC: 228 AN: 395740 Hom.: 1 AF XY: 0.000461 AC XY: 98 AN XY: 212616

African (AFR) AF: 0.0141 AC: 158 AN: 11204

American (AMR) AF: 0.00141 AC: 24 AN: 16998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11740

East Asian (EAS) AF: 0.00 AC: 0 AN: 26018

South Asian (SAS) AF: 0.000184 AC: 8 AN: 43400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23424

Middle Eastern (MID) AF: 0.000591 AC: 1 AN: 1692

European-Non Finnish (NFE) AF: 0.0000461 AC: 11 AN: 238862

Other (OTH) AF: 0.00116 AC: 26 AN: 22402

GnomAD4 genome AF: 0.00461 AC: 681 AN: 147612 Hom.: 3 Cov.: 0 AF XY: 0.00423 AC XY: 303 AN XY: 71708

African (AFR) AF: 0.0158 AC: 633 AN: 40152

American (AMR) AF: 0.00224 AC: 33 AN: 14760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000898 AC: 6 AN: 66826

Other (OTH) AF: 0.00441 AC: 9 AN: 2040

Alfa AF: 0.00 Hom.: 390

ClinVar

Not reported in ClinVar

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

Other links and lift over

dbSNP: rs3062112; hg19: chr3-189675489;