NM_016335.6:c.56C>A

Variant names:

Variant summary

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

The NM_016335.6(PRODH):c.56C>A(p.Pro19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.75 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.293

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.471116E-6).

BP6

Variant 22-18936232-G-T is Benign according to our data. Variant chr22-18936232-G-T is described in ClinVar as [Benign]. Clinvar id is 1168807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18936232-G-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRODH	NM_016335.6 link	c.56C>A	p.Pro19Gln	missense_variant	Exon 1 of 14	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001368250.2 link	c.-114C>A		5_prime_UTR_variant	Exon 1 of 14		NP_001355179.2
PRODH	NM_001195226.2 link	c.-52+158C>A		intron_variant	Intron 1 of 13		NP_001182155.2	O43272

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 link	c.56C>A	p.Pro19Gln	missense_variant	Exon 1 of 14	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 link	c.514-3441G>T		intron_variant	Intron 4 of 5	5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

GnomAD3 exomes

AF:

0.561

AC:

6075

AN:

10824

Hom.:

1655

AF XY:

0.564

AC XY:

3958

AN XY:

7020

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.568

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.894

Gnomad SAS exome

AF:

0.650

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 EAS exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

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

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

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:

0.642

Hom.:

4341

TwinsUK

AF:

0.451

AC:

1672

ALSPAC

AF:

0.465

AC:

1791

ExAC

AF:

0.407

AC:

5137

Asia WGS

AF:

0.668

AC:

2173

AN:

3254

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24842239, 15662599) -

Proline dehydrogenase deficiency

Benign:2

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.8

DANN

Benign

0.89

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.24

T;.

MetaRNN

Benign

0.0000085

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.59

.;N

REVEL

Benign

0.0050

Sift

Benign

0.37

.;T

Sift4G

Uncertain

0.043

D;D

Vest4

0.088

MPC

0.39

ClinPred

0.0021

GERP RS

-0.024

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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