Variant 10-73047065-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001017962.3(P4HA1):c.937C>T(p.His313Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00064 in 1,613,678 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 4 hom. )

Consequence

P4HA1
NM_001017962.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.25

Variant links:

Genes affected

P4HA1 (HGNC:8546): (prolyl 4-hydroxylase subunit alpha 1) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

P4HA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007511109).

BP6

Variant 10-73047065-G-A is Benign according to our data. Variant chr10-73047065-G-A is described in ClinVar as [Benign]. Clinvar id is 3038341.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
P4HA1	NM_001017962.3 linkuse as main transcript	c.937C>T	p.His313Tyr	missense_variant	8/15	ENST00000394890.7
P4HA1	NM_000917.4 linkuse as main transcript	c.937C>T	p.His313Tyr	missense_variant	8/15
P4HA1	NM_001142595.2 linkuse as main transcript	c.937C>T	p.His313Tyr	missense_variant	9/16
P4HA1	NM_001142596.2 linkuse as main transcript	c.937C>T	p.His313Tyr	missense_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA1	ENST00000394890.7 linkuse as main transcript	c.937C>T	p.His313Tyr	missense_variant	8/15	1	NM_001017962.3	A1	P13674-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

530

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000979

AC:

246

AN:

251352

Hom.:

AF XY:

0.000751

AC XY:

102

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000339

AC:

495

AN:

1461440

Hom.:

Cov.:

AF XY:

0.000272

AC XY:

198

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0123

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00353

AC:

538

AN:

152238

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

252

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.000393

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:

0.00189

Alfa

AF:

0.000528

Hom.:

Bravo

AF:

0.00391

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00117

AC:

142

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

P4HA1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.27

T;.;T;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.88

MetaRNN

Benign

0.0075

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.25

N;N;N;N;N

MutationTaster

Benign

0.79

D;D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.040

N;N;N;N;N

REVEL

Benign

0.084

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.29

MVP

0.26

ClinPred

0.015

GERP RS

5.9

Varity_R

0.041

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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