Variant rs4819756 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016335.6(PRODH):c.553T>C(p.Trp185Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W185Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

PRODH (HGNC:9453): (proline dehydrogenase 1) This gene encodes a mitochondrial protein that catalyzes the first step in proline degradation. Mutations in this gene are associated with hyperprolinemia type 1 and susceptibility to schizophrenia 4 (SCZD4). This gene is located on chromosome 22q11.21, a region which has also been associated with the contiguous gene deletion syndromes, DiGeorge and CATCH22. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

PRODH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1503014E-6).

BP6

Variant 22-18925165-A-G is Benign according to our data. Variant chr22-18925165-A-G is described in ClinVar as [Benign]. Clinvar id is 1168806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18925165-A-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRODH	NM_016335.6 linkuse as main transcript	c.553T>C	p.Trp185Arg	missense_variant	4/14	ENST00000357068.11
PRODH	NM_001195226.2 linkuse as main transcript	c.229T>C	p.Trp77Arg	missense_variant	4/14
PRODH	NM_001368250.2 linkuse as main transcript	c.229T>C	p.Trp77Arg	missense_variant	4/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.553T>C	p.Trp185Arg	missense_variant	4/14	1	NM_016335.6	P3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

550

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.638

AC:

160209

AN:

251168

Hom.:

53191

AF XY:

0.634

AC XY:

86073

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.867

Gnomad AMR exome

AF:

0.622

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.967

Gnomad SAS exome

AF:

0.680

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.620

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000312

AC:

AN:

25616

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

14212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000364

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

272

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:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.585

Hom.:

54256

TwinsUK

AF:

0.553

AC:

2051

ALSPAC

AF:

0.568

AC:

2189

ESP6500AA

AF:

0.862

AC:

3798

ESP6500EA

AF:

0.578

AC:

4967

ExAC

AF:

0.641

AC:

77877

Asia WGS

AF:

0.803

AC:

2793

AN:

3478

EpiCase

AF:

0.593

EpiControl

AF:

0.596

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Proline dehydrogenase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.3

DANN

Benign

0.22

DEOGEN2

Benign

0.0026

T;.;.;T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.0069

T;.;T;.;T

MetaRNN

Benign

0.0000012

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

3.7

.;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.50

.;T;T;T;T

Sift4G

Benign

0.53

T;T;T;T;T

Polyphen

0.0

.;B;B;.;.

Vest4

0.033

MutPred

0.32

.;Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);.;.;

MPC

0.48

ClinPred

0.0018

GERP RS

2.9

gMVP

0.36

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