Variant rs193919334 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_016335.6(PRODH):c.1561C>T(p.Arg521Trp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R521Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00014 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62

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:

ENSG00000283809 (HGNC:):

ENSG00000283809 links:

DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

DGCR6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31642967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRODH	NM_016335.6 linkuse as main transcript	c.1561C>T	p.Arg521Trp	missense_variant	13/14	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001195226.2 linkuse as main transcript	c.1237C>T	p.Arg413Trp	missense_variant	13/14		NP_001182155.2	O43272
PRODH	NM_001368250.2 linkuse as main transcript	c.1237C>T	p.Arg413Trp	missense_variant	13/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.1561C>T	p.Arg521Trp	missense_variant	13/14	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 linkuse as main transcript	c.513+2464G>A		intron_variant		5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

24758

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 MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000102

AC:

AN:

196136

Hom.:

AF XY:

0.0000190

AC XY:

AN XY:

105138

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:

0.00

Gnomad NFE exome

AF:

0.0000240

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000137

AC:

AN:

182794

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

91422

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:

0.00

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.000247

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

24758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

12070

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

ExAC

AF:

0.0000251

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

D;.;D;.

M_CAP

Benign

0.074

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-0.93

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.9

.;N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.020

.;D;D;D

Sift4G

Uncertain

0.024

D;D;D;D

Polyphen

0.84

.;P;P;.

Vest4

0.19

MutPred

0.50

.;Loss of disorder (P = 0.0551);Loss of disorder (P = 0.0551);.;

MVP

0.37

MPC

0.56

ClinPred

0.85

GERP RS

3.5

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over