Variant 11-74268196-C-G 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_182904.5(P4HA3):c.1513G>C(p.Asp505His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000902 in 1,614,108 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00077 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 5 hom. )

Consequence

P4HA3
NM_182904.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

P4HA3 (HGNC:30135): (prolyl 4-hydroxylase subunit alpha 3) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

P4HA3 links:

P4HA3 (HGNC:):

P4HA3 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=0.044900894).

BP6

Variant 11-74268196-C-G is Benign according to our data. Variant chr11-74268196-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642147.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P4HA3	NM_182904.5 linkuse as main transcript	c.1513G>C	p.Asp505His	missense_variant	12/13	ENST00000331597.9	NP_878907.1	Q7Z4N8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P4HA3	ENST00000331597.9 linkuse as main transcript	c.1513G>C	p.Asp505His	missense_variant	12/13	1	NM_182904.5	ENSP00000332170.4		Q7Z4N8-1

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000928

AC:

233

AN:

251184

Hom.:

AF XY:

0.00112

AC XY:

152

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000915

AC:

1338

AN:

1461786

Hom.:

Cov.:

AF XY:

0.000985

AC XY:

716

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.000926

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152322

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000777

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000988

AC:

120

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

P4HA3: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.034

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.48

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.55

MVP

0.67

MPC

0.40

ClinPred

0.12

GERP RS

3.9

Varity_R

0.74

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