Variant 22-18913192-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016335.6(PRODH):c.1786T>C(p.Phe596Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.128

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRODH	NM_016335.6 linkuse as main transcript	c.1786T>C	p.Phe596Leu	missense_variant	14/14	ENST00000357068.11
PRODH	NM_001195226.2 linkuse as main transcript	c.1462T>C	p.Phe488Leu	missense_variant	14/14
PRODH	NM_001368250.2 linkuse as main transcript	c.1462T>C	p.Phe488Leu	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.1786T>C	p.Phe596Leu	missense_variant	14/14	1	NM_016335.6	P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

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

AF:

0.00

AC:

AN:

418122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

206064

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Proline dehydrogenase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Aug 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

Cadd

Benign

8.4

Dann

Benign

0.91

DEOGEN2

Benign

0.059

T;.;.;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.59

T;.;T;.

M_CAP

Benign

0.0088

MetaRNN

Benign

0.097

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.81

D;D;D

PrimateAI

Uncertain

0.51

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.0010

.;B;B;.

Vest4

0.013

MutPred

0.28

Gain of disorder (P = 0.0227);.;.;Gain of disorder (P = 0.0227);

MVP

0.048

MPC

0.33

ClinPred

0.18

GERP RS

2.3

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over