Variant rs11913840 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1BP6_Very_Strong

The NM_016335.6(PRODH):c.554G>A(p.Trp185Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0560

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 Uncertain_significance. Variant got 0 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 22-18925164-C-T is Benign according to our data. Variant chr22-18925164-C-T is described in ClinVar as [Benign]. Clinvar id is 459918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18925164-C-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRODH	NM_016335.6 linkuse as main transcript	c.554G>A	p.Trp185Ter	stop_gained	4/14	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2 linkuse as main transcript	c.230G>A	p.Trp77Ter	stop_gained	4/14		NP_001182155.2
PRODH	NM_001368250.2 linkuse as main transcript	c.230G>A	p.Trp77Ter	stop_gained	4/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.554G>A	p.Trp185Ter	stop_gained	4/14	1	NM_016335.6	ENSP00000349577	P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0391

AC:

9822

AN:

251302

Hom.:

272

AF XY:

0.0378

AC XY:

5141

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0339

Gnomad ASJ exome

AF:

0.0470

Gnomad EAS exome

AF:

0.0296

Gnomad SAS exome

AF:

0.0241

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.0375

Gnomad OTH exome

AF:

0.0530

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000378

AC:

AN:

26422

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

14652

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:

0.0000707

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0403

Hom.:

223

TwinsUK

AF:

0.0380

AC:

141

ALSPAC

AF:

0.0363

AC:

140

ESP6500AA

AF:

0.101

AC:

445

ESP6500EA

AF:

0.0364

AC:

313

ExAC

AF:

0.0399

AC:

4849

Asia WGS

AF:

0.0450

AC:

155

AN:

3478

EpiCase

AF:

0.0432

EpiControl

AF:

0.0412

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Proline dehydrogenase deficiency;C1833247:Schizophrenia 4

Benign:1

Benign, criteria provided, single submitter

reference population

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Mar 18, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Benign

0.89

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.050

MutationTaster

Benign

1.5e-18

P;P;P

Vest4

0.58

GERP RS

-6.1

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