rs35500164

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_022356.4(P3H1):c.1716C>T(p.Ile572Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,611,888 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I572I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 10 hom. )

Consequence

P3H1
NM_022356.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.134

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-42750190-G-A is Benign according to our data. Variant chr1-42750190-G-A is described in ClinVar as [Benign]. Clinvar id is 386781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.134 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00522 (794/152158) while in subpopulation AFR AF= 0.0184 (763/41488). AF 95% confidence interval is 0.0173. There are 10 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P3H1	NM_022356.4 linkuse as main transcript	c.1716C>T	p.Ile572Ile	synonymous_variant	11/15	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.1716C>T	p.Ile572Ile	synonymous_variant	11/15	1	NM_022356.4	ENSP00000296388.5		Q32P28-1

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

793

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00138

AC:

340

AN:

247038

Hom.:

AF XY:

0.00109

AC XY:

145

AN XY:

133636

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.000557

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000266

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000597

AC:

872

AN:

1459730

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

381

AN XY:

725872

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.000632

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000963

Gnomad4 OTH exome

AF:

0.000945

GnomAD4 genome

AF:

0.00522

AC:

794

AN:

152158

Hom.:

Cov.:

AF XY:

0.00507

AC XY:

377

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00269

Hom.:

Bravo

AF:

0.00625

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Osteogenesis imperfecta type 8

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 02, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

2.7

DANN

Uncertain

0.99

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