Genetic Variant P3H3:c.1560+110C>T (chr12-6837196-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014262.5(P3H3):c.1560+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,037,460 control chromosomes in the GnomAD database, including 43,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6565 hom., cov: 32)

Exomes 𝑓: 0.29 ( 37220 hom. )

Consequence

P3H3
NM_014262.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.44

Publications

6 publications found

Variant links:

Genes affected

P3H3 (HGNC:19318): (prolyl 3-hydroxylase 3) The protein encoded by this gene belongs to the leprecan family of proteoglycans, which function as collagen prolyl hydroxylases that are required for proper collagen biosynthesis, folding and assembly. This protein, like other family members, is thought to reside in the endoplasmic reticulum. Epigenetic inactivation of this gene is associated with breast and other cancers, suggesting that it may function as a tumor suppressor. [provided by RefSeq, Aug 2013]

P3H3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P3H3	NM_014262.5 link	c.1560+110C>T		intron_variant	Intron 10 of 14	ENST00000290510.10	NP_055077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H3	ENST00000290510.10 link	c.1560+110C>T		intron_variant	Intron 10 of 14	1	NM_014262.5	ENSP00000478600.1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44083

AN:

151968

Hom.:

6564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.305

GnomAD4 exome

AF:

0.286

AC:

253033

AN:

885374

Hom.:

37220

Cov.:

AF XY:

0.288

AC XY:

129215

AN XY:

448798

show subpopulations

African (AFR)

AF:

0.269

AC:

5629

AN:

20948

American (AMR)

AF:

0.308

AC:

8283

AN:

26862

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

6144

AN:

18164

East Asian (EAS)

AF:

0.290

AC:

9800

AN:

33800

South Asian (SAS)

AF:

0.332

AC:

20616

AN:

62174

European-Finnish (FIN)

AF:

0.272

AC:

8797

AN:

32322

Middle Eastern (MID)

AF:

0.312

AC:

1020

AN:

3266

European-Non Finnish (NFE)

AF:

0.279

AC:

180469

AN:

647022

Other (OTH)

AF:

0.301

AC:

12275

AN:

40816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

9552

19104

28656

38208

47760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4912

9824

14736

19648

24560

<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:

0.290

AC:

44103

AN:

152086

Hom.:

6565

Cov.:

AF XY:

0.290

AC XY:

21584

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.274

AC:

11389

AN:

41492

American (AMR)

AF:

0.323

AC:

4937

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1214

AN:

3470

East Asian (EAS)

AF:

0.335

AC:

1725

AN:

5152

South Asian (SAS)

AF:

0.332

AC:

1603

AN:

4828

European-Finnish (FIN)

AF:

0.276

AC:

2920

AN:

10578

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19423

AN:

67958

Other (OTH)

AF:

0.309

AC:

652

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1646

3291

4937

6582

8228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.287

Hom.:

20598

Bravo

AF:

0.292

Asia WGS

AF:

0.325

AC:

1127

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

(source)

DANN

Benign

0.67

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over