rs372055

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_016335.6(PRODH):c.1741C>T(p.Leu581Leu) variant causes a synonymous change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000032 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000016 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.17

Publications

30 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 links:

ENSG00000283809 (HGNC:):

ENSG00000283809 links:

DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

DGCR6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 22-18913237-G-A is Benign according to our data. Variant chr22-18913237-G-A is described in ClinVar as Benign. ClinVar VariationId is 127267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PRODH	NM_016335.6 link	c.1741C>T	p.Leu581Leu	synonymous_variant	Exon 14 of 14	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2 link	c.1417C>T	p.Leu473Leu	synonymous_variant	Exon 14 of 14		NP_001182155.2
PRODH	NM_001368250.2 link	c.1417C>T	p.Leu473Leu	synonymous_variant	Exon 14 of 14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 link	c.1741C>T	p.Leu581Leu	synonymous_variant	Exon 14 of 14	1	NM_016335.6	ENSP00000349577.6
ENSG00000283809	ENST00000638240.1 link	c.513+2209G>A		intron_variant	Intron 4 of 5	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

31630

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.783

AC:

125626

AN:

160360

AF XY:

0.789

show subpopulations

Gnomad AFR exome

AF:

0.620

Gnomad AMR exome

AF:

0.762

Gnomad ASJ exome

AF:

0.804

Gnomad EAS exome

AF:

0.840

Gnomad FIN exome

AF:

0.756

Gnomad NFE exome

AF:

0.799

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000158

AC:

AN:

505186

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

248788

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000514

AC:

AN:

19468

American (AMR)

AF:

0.00

AC:

AN:

14488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8962

East Asian (EAS)

AF:

0.00

AC:

AN:

11970

South Asian (SAS)

AF:

0.00

AC:

AN:

26928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2596

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

379274

Other (OTH)

AF:

0.00

AC:

AN:

22142

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000315

AC:

AN:

31716

Hom.:

Cov.:

AF XY:

0.0000650

AC XY:

AN XY:

15382

show subpopulations

African (AFR)

AF:

0.0000671

AC:

AN:

14912

American (AMR)

AF:

0.00

AC:

AN:

2172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

462

East Asian (EAS)

AF:

0.00

AC:

AN:

626

South Asian (SAS)

AF:

0.00

AC:

AN:

756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

10508

Other (OTH)

AF:

0.00

AC:

AN:

368

Alfa

AF:

0.637

Hom.:

15879

Asia WGS

AF:

0.762

AC:

2649

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Proline dehydrogenase deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.3

(source)

DANN

Benign

0.72

PhyloP100

6.2

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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