Variant chr22-18922842-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000357068.11(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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 0)

Consequence

PRODH
ENST00000357068.11 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein
PRODH	NM_016335.6 linkuse as main transcript	c.824C>A	p.Thr275Asn	missense_variant	6/14	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2 linkuse as main transcript	c.500C>A	p.Thr167Asn	missense_variant	6/14		NP_001182155.2
PRODH	NM_001368250.2 linkuse as main transcript	c.500C>A	p.Thr167Asn	missense_variant	6/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.824C>A	p.Thr275Asn	missense_variant	6/14	1	NM_016335.6	ENSP00000349577	P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0644

AC:

16175

AN:

251154

Hom.:

947

AF XY:

0.0596

AC XY:

8093

AN XY:

135812

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 SAS exome

AF:

0.0290

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:

0.0493

Hom.:

191

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 20524212, 25525159, 25569235) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.8

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

MutationTaster

Benign

1.0

P;P;P

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

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