Variant rs16983466 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016335.6(PRODH):c.1278C>T(p.Asp426=) variant causes a synonymous 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 83 hom., cov: 2)

Exomes 𝑓: 0.22 ( 6255 hom. )

Consequence

PRODH
NM_016335.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.632

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 22-18918465-G-A is Benign according to our data. Variant chr22-18918465-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1166601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18918465-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.632 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRODH	NM_016335.6 linkuse as main transcript	c.1278C>T	p.Asp426=	synonymous_variant	11/14	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2 linkuse as main transcript	c.954C>T	p.Asp318=	synonymous_variant	11/14		NP_001182155.2
PRODH	NM_001368250.2 linkuse as main transcript	c.954C>T	p.Asp318=	synonymous_variant	11/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.1278C>T	p.Asp426=	synonymous_variant	11/14	1	NM_016335.6	ENSP00000349577	P3

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

581

AN:

3082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.0839

Gnomad SAS

AF:

0.0991

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.144

AC:

35182

AN:

244830

Hom.:

2689

AF XY:

0.141

AC XY:

18733

AN XY:

132756

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0620

Gnomad SAS exome

AF:

0.0986

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.218

AC:

33724

AN:

154810

Hom.:

6255

Cov.:

AF XY:

0.212

AC XY:

17516

AN XY:

82624

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.223

GnomAD4 genome

AF:

0.189

AC:

583

AN:

3092

Hom.:

Cov.:

AF XY:

0.188

AC XY:

272

AN XY:

1446

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.0854

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.141

Hom.:

728

Asia WGS

AF:

0.110

AC:

384

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Proline dehydrogenase deficiency;C1833247:Schizophrenia 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 22, 2021

- -

Proline dehydrogenase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.19

DANN

Benign

0.89

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