Variant 3-189995416-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018192.4(P3H2):c.507A>G(p.Glu169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,613,294 control chromosomes in the GnomAD database, including 85,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7170 hom., cov: 32)

Exomes 𝑓: 0.32 ( 78185 hom. )

Consequence

P3H2
NM_018192.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.148

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 3-189995416-T-C is Benign according to our data. Variant chr3-189995416-T-C is described in ClinVar as [Benign]. Clinvar id is 677171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189995416-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.148 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P3H2	NM_018192.4 linkuse as main transcript	c.507A>G	p.Glu169=	synonymous_variant	2/15	ENST00000319332.10
P3H2	NM_001134418.2 linkuse as main transcript	c.-37A>G		5_prime_UTR_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P3H2	ENST00000319332.10 linkuse as main transcript	c.507A>G	p.Glu169=	synonymous_variant	2/15	1	NM_018192.4	P1	Q8IVL5-1
P3H2	ENST00000427335.6 linkuse as main transcript	c.-37A>G		5_prime_UTR_variant	2/15	1			Q8IVL5-2
P3H2	ENST00000426003.1 linkuse as main transcript	c.-37A>G		5_prime_UTR_variant	2/4	4
P3H2	ENST00000444866.5 linkuse as main transcript	c.-37A>G		5_prime_UTR_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45430

AN:

151796

Hom.:

7160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.335

AC:

84110

AN:

250906

Hom.:

14856

AF XY:

0.336

AC XY:

45537

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.493

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.323

AC:

472153

AN:

1461380

Hom.:

78185

Cov.:

AF XY:

0.324

AC XY:

235206

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.344

Gnomad4 FIN exome

AF:

0.432

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.299

AC:

45455

AN:

151914

Hom.:

7170

Cov.:

AF XY:

0.305

AC XY:

22641

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.484

Gnomad4 SAS

AF:

0.353

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.301

Hom.:

3163

Bravo

AF:

0.287

Asia WGS

AF:

0.358

AC:

1243

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Myopia, high, with cataract and vitreoretinal degeneration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.2

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over