chr3-189957700-A-AAGAGAG

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_018192.4(P3H2):​c.*206_*211dupCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.046 (0 hom.)
• Consequence: P3H2 NM_018192.4 3_prime_UTR
• Clinical Significance: Likely 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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 3-189957700-A-AAGAGAG is Benign according to our data. Variant chr3-189957700-A-AAGAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 1220167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0463 (17936/387722) while in subpopulation MID AF = 0.0513 (85/1658). AF 95% confidence interval is 0.0492. There are 0 homozygotes in GnomAdExome4. There are 9699 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*206_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*206_*211dupCTCTCT		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_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5
P3H2	ENST00000427335.6	c.*206_*211dupCTCTCT		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2
P3H2	ENST00000490940.1	n.463_468dupCTCTCT		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.000984 AC: 145 AN: 147284 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000849

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.000543

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00694

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000479

Gnomad OTH AF: 0.000992

GnomAD4 exome AF: 0.0463 AC: 17936 AN: 387722 Hom.: 0 Cov.: 0 AF XY: 0.0466 AC XY: 9699 AN XY: 208308

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

African (AFR) AF: 0.00832 AC: 93 AN: 11178

American (AMR) AF: 0.0385 AC: 644 AN: 16724

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 346 AN: 11592

East Asian (EAS) AF: 0.0156 AC: 404 AN: 25872

South Asian (SAS) AF: 0.0477 AC: 2014 AN: 42194

European-Finnish (FIN) AF: 0.0736 AC: 1676 AN: 22764

Middle Eastern (MID) AF: 0.0513 AC: 85 AN: 1658

European-Non Finnish (NFE) AF: 0.0499 AC: 11668 AN: 233710

Other (OTH) AF: 0.0457 AC: 1006 AN: 22030

⚠️ 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: 0.000997 AC: 147 AN: 147394 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 77 AN XY: 71574

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

African (AFR) AF: 0.000872 AC: 35 AN: 40150

American (AMR) AF: 0.000543 AC: 8 AN: 14742

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3414

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

South Asian (SAS) AF: 0.000220 AC: 1 AN: 4536

European-Finnish (FIN) AF: 0.00694 AC: 67 AN: 9656

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

European-Non Finnish (NFE) AF: 0.000479 AC: 32 AN: 66756

Other (OTH) AF: 0.000982 AC: 2 AN: 2036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 390

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 24, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Publications

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Other links and lift over

dbSNP: rs3062112; hg19: chr3-189675489; COSMIC: COSV60019318;