Variant rs5992333 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.1440C>T(p.Tyr480Tyr) 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 Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1568 hom., cov: 0)

Exomes 𝑓: 0.057 ( 3950 hom. )

Consequence

PRODH
NM_016335.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.06

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:

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=-0.47).

BP6

Variant 22-18916976-G-A is Benign according to our data. Variant chr22-18916976-G-A is described in ClinVar as [Benign]. Clinvar id is 459912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRODH	NM_016335.6 linkuse as main transcript	c.1440C>T	p.Tyr480Tyr	synonymous_variant	12/14	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001195226.2 linkuse as main transcript	c.1116C>T	p.Tyr372Tyr	synonymous_variant	12/14		NP_001182155.2	O43272
PRODH	NM_001368250.2 linkuse as main transcript	c.1116C>T	p.Tyr372Tyr	synonymous_variant	12/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.1440C>T	p.Tyr480Tyr	synonymous_variant	12/14	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 linkuse as main transcript	c.513+5948G>A		intron_variant		5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

3912

AN:

35166

Hom.:

1561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0977

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.00997

AC:

2502

AN:

250904

Hom.:

AF XY:

0.00873

AC XY:

1184

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.0579

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.0510

Gnomad SAS exome

AF:

0.00755

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00718

GnomAD4 exome

AF:

0.0575

AC:

8831

AN:

153698

Hom.:

3950

Cov.:

AF XY:

0.0550

AC XY:

4344

AN XY:

78924

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.00628

Gnomad4 EAS exome

AF:

0.415

Gnomad4 SAS exome

AF:

0.0661

Gnomad4 FIN exome

AF:

0.000501

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.111

AC:

3925

AN:

35274

Hom.:

1568

Cov.:

AF XY:

0.111

AC XY:

1880

AN XY:

16876

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.0978

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.0671

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.00685

Hom.:

159

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00243

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	Jun 10, 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

-0.47

CADD

Benign

1.4

DANN

Benign

0.85

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