chr3-189957700-A-AAGAGAG

Position:

• chr3-189957700-A-AAGAGAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_018192.4(P3H2):​c.*211_*212insCTCTCT 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

Verdict is Likely_benign. Variant got -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. gnomad4_exome 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 gnomad4_exome. There are 9699 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*211_*212insCTCTCT		3_prime_UTR_variant	15/15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*211_*212insCTCTCT		3_prime_UTR_variant	15/15		NP_001127890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H2	ENST00000319332.10	c.*211_*212insCTCTCT		3_prime_UTR_variant	15/15	1	NM_018192.4	ENSP00000316881	P1
P3H2	ENST00000427335.6	c.*211_*212insCTCTCT		3_prime_UTR_variant	15/15	1		ENSP00000408947
P3H2	ENST00000490940.1	n.468_469insCTCTCT		non_coding_transcript_exon_variant	2/2	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

Gnomad4 AFR exome AF: 0.00832

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.0156

Gnomad4 SAS exome AF: 0.0477

Gnomad4 FIN exome AF: 0.0736

Gnomad4 NFE exome AF: 0.0499

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.000997 AC: 147 AN: 147394 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 77 AN XY: 71574

Gnomad4 AFR AF: 0.000872

Gnomad4 AMR AF: 0.000543

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.00694

Gnomad4 NFE AF: 0.000479

Gnomad4 OTH AF: 0.000982

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2019

- -

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;