Variant 12-6839364-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.2114T>C(p.Met705Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,553,340 control chromosomes in the GnomAD database, including 333 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 0.0042 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 304 hom. )

Consequence

P3H3
NM_014262.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.630

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015749931).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0944 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.2114T>C	p.Met705Thr	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.2114T>C	p.Met705Thr	missense_variant	15/15	1	NM_014262.5	ENSP00000478600.1	Q8IVL6-1
P3H3	ENST00000612048.4 linkuse as main transcript	n.1647T>C		non_coding_transcript_exon_variant	14/14	1
P3H3	ENST00000536140.5 linkuse as main transcript	n.2744T>C		non_coding_transcript_exon_variant	16/16	2

Frequencies

GnomAD3 genomes

AF:

0.00416

AC:

631

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.00831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00911

AC:

1459

AN:

160148

Hom.:

AF XY:

0.00909

AC XY:

768

AN XY:

84480

show subpopulations

Gnomad AFR exome

AF:

0.000948

Gnomad AMR exome

AF:

0.000281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.115

Gnomad SAS exome

AF:

0.00629

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000949

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00396

AC:

5554

AN:

1401414

Hom.:

304

Cov.:

AF XY:

0.00394

AC XY:

2725

AN XY:

691366

show subpopulations

Gnomad4 AFR exome

AF:

0.000347

Gnomad4 AMR exome

AF:

0.000223

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.00601

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000463

Gnomad4 OTH exome

AF:

0.00737

GnomAD4 genome

AF:

0.00417

AC:

633

AN:

151926

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

358

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.00852

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.000910

Hom.:

Bravo

AF:

0.00494

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000728

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00450

AC:

468

Asia WGS

AF:

0.0500

AC:

172

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.5

DANN

Benign

0.71

DEOGEN2

Benign

0.10

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

REVEL

Benign

0.061

Sift4G

Benign

0.43

Polyphen

0.0

Vest4

0.095

MVP

0.014

ClinPred

0.0012

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.33

gMVP

0.19

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