3-189957700-A-AAGAG

Position:

• chr3-189957700-A-AAGAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 3-189957700-A-AAGAG is Benign according to our data. Variant chr3-189957700-A-AAGAG is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H2	NM_018192.4	c.*211_*212insCTCT		3_prime_UTR_variant	15/15	ENST00000319332.10	NP_060662.2
P3H2	NM_001134418.2	c.*211_*212insCTCT		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_*212insCTCT		3_prime_UTR_variant	15/15	1	NM_018192.4	ENSP00000316881	P1
P3H2	ENST00000427335.6	c.*211_*212insCTCT		3_prime_UTR_variant	15/15	1		ENSP00000408947
P3H2	ENST00000490940.1	n.468_469insCTCT		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 AFR exome AF: 0.0557

Gnomad4 AMR exome AF: 0.00793

Gnomad4 ASJ exome AF: 0.00248

Gnomad4 EAS exome AF: 0.00582

Gnomad4 SAS exome AF: 0.00336

Gnomad4 FIN exome AF: 0.00745

Gnomad4 NFE exome AF: 0.00572

Gnomad4 OTH exome AF: 0.0106

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

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.000879

Gnomad4 EAS AF: 0.00625

Gnomad4 SAS AF: 0.00243

Gnomad4 FIN AF: 0.00308

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 06, 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;