Variant 12-6839304-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014262.5(P3H3):c.2054T>C(p.Ile685Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,552,430 control chromosomes in the GnomAD database, including 104,063 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10210 hom., cov: 31)

Exomes 𝑓: 0.36 ( 93853 hom. )

Consequence

P3H3
NM_014262.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.698

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:

P3H3 (HGNC:):

P3H3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015980005).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H3	NM_014262.5 linkuse as main transcript	c.2054T>C	p.Ile685Thr	missense_variant	15/15	ENST00000290510.10	NP_055077.2	Q8IVL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
P3H3	ENST00000290510.10 linkuse as main transcript	c.2054T>C	p.Ile685Thr	missense_variant	15/15	1	NM_014262.5	ENSP00000478600.1	Q8IVL6-1
P3H3	ENST00000612048.4 linkuse as main transcript	n.1587T>C		non_coding_transcript_exon_variant	14/14	1
P3H3	ENST00000536140.5 linkuse as main transcript	n.2684T>C		non_coding_transcript_exon_variant	16/16	2

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55160

AN:

151358

Hom.:

10205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.364

GnomAD3 exomes

AF:

0.359

AC:

57177

AN:

159106

Hom.:

10423

AF XY:

0.361

AC XY:

30362

AN XY:

83996

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.373

Gnomad EAS exome

AF:

0.397

Gnomad SAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.364

AC:

510462

AN:

1400954

Hom.:

93853

Cov.:

AF XY:

0.365

AC XY:

252099

AN XY:

691178

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.369

Gnomad4 EAS exome

AF:

0.372

Gnomad4 SAS exome

AF:

0.381

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.364

AC:

55185

AN:

151476

Hom.:

10210

Cov.:

AF XY:

0.363

AC XY:

26849

AN XY:

73982

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.373

Gnomad4 EAS

AF:

0.392

Gnomad4 SAS

AF:

0.369

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.369

Alfa

AF:

0.349

Hom.:

19585

Bravo

AF:

0.367

TwinsUK

AF:

0.365

AC:

1353

ALSPAC

AF:

0.371

AC:

1430

ESP6500AA

AF:

0.358

AC:

1469

ESP6500EA

AF:

0.340

AC:

2851

ExAC

AF:

0.268

AC:

26023

Asia WGS

AF:

0.371

AC:

1286

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.14

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.92

REVEL

Benign

0.076

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.014

ClinPred

0.00092

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.029

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over