rs146648839

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.172G>A(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A58A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 0)

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.26

Publications

6 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=0.0018523335).

BP6

Variant 22-18936116-C-T is Benign according to our data. Variant chr22-18936116-C-T is described in ClinVar as Benign. ClinVar VariationId is 459914.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.172G>A	p.Ala58Thr	missense_variant	Exon 1 of 14	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001195226.2 link	c.-52+274G>A		intron_variant	Intron 1 of 13		NP_001182155.2	O43272
PRODH	NM_001368250.2 link	c.-52+54G>A		intron_variant	Intron 1 of 13		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 link	c.172G>A	p.Ala58Thr	missense_variant	Exon 1 of 14	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 link	c.514-3557C>T		intron_variant	Intron 4 of 5	5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

AC:

AN:

Hom.:

Cov.:

GnomAD2 exomes

AF:

0.0188

AC:

1324

AN:

70306

AF XY:

0.0174

show subpopulations

Gnomad AFR exome

AF:

0.0614

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0441

GnomAD4 exome

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

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GnomAD4 genome

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

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Alfa

AF:

0.0194

Hom.:

TwinsUK

AF:

0.0278

AC:

103

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.0296

AC:

ESP6500EA

AF:

0.0120

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ExAC

AF:

0.00606

AC:

184

Asia WGS

AF:

0.00726

AC:

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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: 20524212, 24842239) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Proline dehydrogenase deficiency

Benign:1

Feb 02, 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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.053

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.64

T;.

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

PhyloP100

-1.3

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.13

.;N

REVEL

Benign

0.015

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Vest4

0.017

MPC

0.27

ClinPred

0.0054

GERP RS

-4.3

PromoterAI

0.043

Neutral

(source)

gMVP

0.20

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