Variant 22-18913355-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000357068.11(PRODH):c.1623C>T(p.Ala541=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A541A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.23 ( 2524 hom., cov: 0)

Exomes 𝑓: 0.28 ( 39173 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
ENST00000357068.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.85

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:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 22-18913355-G-A is Benign according to our data. Variant chr22-18913355-G-A is described in ClinVar as [Benign]. Clinvar id is 1166479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRODH	NM_016335.6 linkuse as main transcript	c.1623C>T	p.Ala541=	synonymous_variant	14/14	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2 linkuse as main transcript	c.1299C>T	p.Ala433=	synonymous_variant	14/14		NP_001182155.2
PRODH	NM_001368250.2 linkuse as main transcript	c.1299C>T	p.Ala433=	synonymous_variant	14/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.1623C>T	p.Ala541=	synonymous_variant	14/14	1	NM_016335.6	ENSP00000349577	P3

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

5419

AN:

23908

Hom.:

2525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.100

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.0299

AC:

5176

AN:

173232

Hom.:

107

AF XY:

0.0311

AC XY:

2873

AN XY:

92430

show subpopulations

Gnomad AFR exome

AF:

0.00648

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0294

Gnomad EAS exome

AF:

0.000468

Gnomad SAS exome

AF:

0.0405

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.0412

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.278

AC:

86121

AN:

309388

Hom.:

39173

Cov.:

AF XY:

0.277

AC XY:

43203

AN XY:

155900

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.0669

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.000938

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.226

AC:

5419

AN:

23970

Hom.:

2524

Cov.:

AF XY:

0.214

AC XY:

2481

AN XY:

11612

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.542

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.539

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.0338

Hom.:

115

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

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_noAF

Benign

-0.55

CADD

Benign

1.6

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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