22-18922842-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016335.6(PRODH):c.824C>A(p.Thr275Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: not found (cov: 0)

Consequence

PRODH
NM_016335.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

hyperprolinemia type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)

PRODH links:

ENSG00000283809 (HGNC:):

ENSG00000283809 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017009974).

BP6

Variant 22-18922842-G-T is Benign according to our data. Variant chr22-18922842-G-T is described in ClinVar as [Benign]. Clinvar id is 1168805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRODH	NM_016335.6 link	c.824C>A	p.Thr275Asn	missense_variant	Exon 6 of 14	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001195226.2 link	c.500C>A	p.Thr167Asn	missense_variant	Exon 6 of 14		NP_001182155.2	O43272
PRODH	NM_001368250.2 link	c.500C>A	p.Thr167Asn	missense_variant	Exon 6 of 14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 link	c.824C>A	p.Thr275Asn	missense_variant	Exon 6 of 14	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 link	c.513+11814G>T		intron_variant	Intron 4 of 5	5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0644

AC:

16175

AN:

251154

AF XY:

0.0596

show subpopulations

Gnomad AFR exome

AF:

0.00942

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0725

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0613

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0470

Hom.:

337

TwinsUK

AF:

0.0437

AC:

162

ALSPAC

AF:

0.0462

AC:

178

ESP6500AA

AF:

0.0150

AC:

ESP6500EA

AF:

0.0427

AC:

367

ExAC

AF:

0.0577

AC:

7002

Asia WGS

AF:

0.0870

AC:

301

AN:

3478

EpiCase

AF:

0.0493

EpiControl

AF:

0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 20524212, 25525159, 25569235) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Proline dehydrogenase deficiency

Benign:1

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

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.8

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.012

T;.;.;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.76

T;.;T;.;T

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.27

.;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.60

.;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T

Polyphen

0.37

.;B;B;.;.

Vest4

0.19

MPC

0.33

ClinPred

0.0037

GERP RS

0.76

gMVP

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over