Genetic Variant NM_018192.4:c.*194_*211dupCTCTCTCTCTCTCTCTCT (chr3-189957700-A-AAGAGAGAGAGAGAGAGAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018192.4(P3H2):c.*194_*211dupCTCTCTCTCTCTCTCTCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

P3H2
NM_018192.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H2	NM_018192.4 link	c.194_211dupCTCTCTCTCTCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15	ENST00000319332.10	NP_060662.2	Q8IVL5-1
P3H2	NM_001134418.2 link	c.194_211dupCTCTCTCTCTCTCTCTCT		3_prime_UTR_variant	Exon 15 of 15		NP_001127890.1	Q8IVL5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
P3H2	ENST00000319332.10 link	c.194_211dupCTCTCTCTCTCTCTCTCT	3_prime_UTR_variant	Exon 15 of 15	1	NM_018192.4	ENSP00000316881.5	Q8IVL5-1
P3H2	ENST00000427335.6 link	c.194_211dupCTCTCTCTCTCTCTCTCT	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000408947.2	Q8IVL5-2
P3H2	ENST00000490940.1 link	n.451_468dupCTCTCTCTCTCTCTCTCT	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

395774

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

212638

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

11232

American (AMR)

AF:

0.0000588

AC:

AN:

17000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11740

East Asian (EAS)

AF:

0.00

AC:

AN:

26018

South Asian (SAS)

AF:

0.00

AC:

AN:

43404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23424

Middle Eastern (MID)

AF:

0.000591

AC:

AN:

1692

European-Non Finnish (NFE)

AF:

0.0000293

AC:

AN:

238862

Other (OTH)

AF:

0.00

AC:

AN:

22402

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000004), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000136

AC:

AN:

147502

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71586

show subpopulations

African (AFR)

AF:

0.0000250

AC:

AN:

40034

American (AMR)

AF:

0.00

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

4970

South Asian (SAS)

AF:

0.00

AC:

AN:

4542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66832

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Splicing

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

Publications

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NM_018192.4:c.194_211dupCTCTCTCTCTCTCTCTCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over