Variant chr22-18936116-C-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 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. 11/17 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: 𝑓 0.0 ( 0 hom., 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

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:

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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=0.0018523335).

BP6

Variant 22-18936116-C-T is Benign according to our data. Variant chr22-18936116-C-T is described in ClinVar as [Benign]. Clinvar id is 459914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRODH	NM_016335.6 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/14	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001195226.2 linkuse as main transcript	c.-52+274G>A		intron_variant			NP_001182155.2	O43272
PRODH	NM_001368250.2 linkuse as main transcript	c.-52+54G>A		intron_variant			NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/14	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 linkuse as main transcript	c.514-3557C>T		intron_variant		5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

GnomAD3 exomes

AF:

0.0188

AC:

1324

AN:

70306

Hom.:

AF XY:

0.0174

AC XY:

713

AN XY:

40932

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 SAS exome

AF:

0.00482

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

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

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

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0132

Hom.:

TwinsUK

AF:

0.0278

AC:

103

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.0296

AC:

ESP6500EA

AF:

0.0120

AC:

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 20524212, 24842239) -

Proline dehydrogenase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.053

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

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

gMVP

0.20

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