Variant 1-42746710-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_022356.4(P3H1):c.2198A>G(p.Lys733Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,551,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 1 hom. )

Consequence

P3H1
NM_022356.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

P3H1 (HGNC:19316): (prolyl 3-hydroxylase 1) This gene encodes an enzyme that is a member of the collagen prolyl hydroxylase family. These enzymes are localized to the endoplasmic reticulum and their activity is required for proper collagen synthesis and assembly. Mutations in this gene are associated with osteogenesis imperfecta type VIII. Three alternatively spliced transcript variants encoding different isoforms have been described. Other variants may exist, but their biological validity has not been determined. [provided by RefSeq, Aug 2011]

P3H1 links:

P3H1 (HGNC:):

P3H1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0063889027).

BP6

Variant 1-42746710-T-C is Benign according to our data. Variant chr1-42746710-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 727990.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H1	NM_022356.4 linkuse as main transcript	c.2198A>G	p.Lys733Arg	missense_variant	15/15	ENST00000296388.10	NP_071751.3	Q32P28-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P3H1	ENST00000296388.10 linkuse as main transcript	c.2198A>G	p.Lys733Arg	missense_variant	15/15	1	NM_022356.4	ENSP00000296388.5		Q32P28-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

155822

Hom.:

AF XY:

0.000242

AC XY:

AN XY:

82562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000908

AC:

127

AN:

1399416

Hom.:

Cov.:

AF XY:

0.0000913

AC XY:

AN XY:

690236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.00000741

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.000210

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000529

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000915

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.52

M_CAP

Benign

0.0075

MetaRNN

Benign

0.0064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PROVEAN

Benign

-0.18

REVEL

Benign

0.011

Sift

Benign

0.052

Sift4G

Benign

0.27

Polyphen

0.0030

Vest4

0.068

MVP

0.31

ClinPred

0.024

GERP RS

0.045

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over