3-189957700-AAGAGAG-A

Variant names:

• chr3-189957700-AAGAGAG-A
• rs3062112
• NM_018192.4:c.*206_*211delCTCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018192.4(P3H2):​c.*206_*211delCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000481 in 542,768 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00064 (0 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: G2P, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*206_*211delCTCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*206_*211delCTCTCT		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	ENST00000319332.10	c.*206_*211delCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.*206_*211delCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2
P3H2	ENST00000490940.1	n.463_468delCTCTCT		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0000678 AC: 10 AN: 147494 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000678

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000748

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000635 AC: 251 AN: 395166 Hom.: 0 AF XY: 0.000565 AC XY: 120 AN XY: 212320

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

African (AFR) AF: 0.00657 AC: 72 AN: 10958

American (AMR) AF: 0.0000589 AC: 1 AN: 16986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11732

East Asian (EAS) AF: 0.000308 AC: 8 AN: 26000

South Asian (SAS) AF: 0.000438 AC: 19 AN: 43350

European-Finnish (FIN) AF: 0.000171 AC: 4 AN: 23410

Middle Eastern (MID) AF: 0.00118 AC: 2 AN: 1688

European-Non Finnish (NFE) AF: 0.000524 AC: 125 AN: 238666

Other (OTH) AF: 0.000894 AC: 20 AN: 22376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000677 AC: 10 AN: 147602 Hom.: 0 Cov.: 0 AF XY: 0.0000558 AC XY: 4 AN XY: 71702

African (AFR) AF: 0.0000747 AC: 3 AN: 40142

American (AMR) AF: 0.0000678 AC: 1 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: 0.000220 AC: 1 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: 0.0000748 AC: 5 AN: 66826

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.00 Hom.: 390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;