3-189995416-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018192.4(P3H2):c.507A>G(p.Glu169Glu) 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:4

Conservation

PhyloP100: 0.148

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

myopia, high, with cataract and vitreoretinal degeneration
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

P3H2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 677171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3H2	NM_018192.4	MANE Select	c.507A>G	p.Glu169Glu	synonymous	Exon 2 of 15	NP_060662.2
	P3H2	NM_001134418.2		c.-37A>G		5_prime_UTR	Exon 2 of 15	NP_001127890.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
P3H2	ENST00000319332.10	TSL:1 MANE Select	c.507A>G	p.Glu169Glu	synonymous	Exon 2 of 15	ENSP00000316881.5
P3H2	ENST00000427335.6	TSL:1	c.-37A>G		5_prime_UTR	Exon 2 of 15	ENSP00000408947.2
P3H2	ENST00000444866.5	TSL:4	c.-37A>G		5_prime_UTR	Exon 2 of 4	ENSP00000391374.1

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

GnomAD2 exomes

AF:

0.335

AC:

84110

AN:

250906

AF XY:

0.336

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 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

African (AFR)

AF:

0.212

AC:

7082

AN:

33478

American (AMR)

AF:

0.320

AC:

14304

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

6302

AN:

26134

East Asian (EAS)

AF:

0.481

AC:

19107

AN:

39690

South Asian (SAS)

AF:

0.344

AC:

29665

AN:

86252

European-Finnish (FIN)

AF:

0.432

AC:

22994

AN:

53202

Middle Eastern (MID)

AF:

0.264

AC:

1521

AN:

5768

European-Non Finnish (NFE)

AF:

0.317

AC:

351961

AN:

1111748

Other (OTH)

AF:

0.318

AC:

19217

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16298

32596

48895

65193

81491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11496

22992

34488

45984

57480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

45455

AN:

151914

Hom.:

7170

Cov.:

AF XY:

0.305

AC XY:

22641

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.211

AC:

8746

AN:

41452

American (AMR)

AF:

0.310

AC:

4736

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

817

AN:

3472

East Asian (EAS)

AF:

0.484

AC:

2492

AN:

5146

South Asian (SAS)

AF:

0.353

AC:

1701

AN:

4818

European-Finnish (FIN)

AF:

0.427

AC:

4489

AN:

10508

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21675

AN:

67944

Other (OTH)

AF:

0.274

AC:

579

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1595

3189

4784

6378

7973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.300

Hom.:

3178

Bravo

AF:

0.287

Asia WGS

AF:

0.358

AC:

1243

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Apr 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Myopia, high, with cataract and vitreoretinal degeneration

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.2

(source)

DANN

Benign

0.77

PhyloP100

0.15

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over