chr22-18913156-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016335.6(PRODH):c.*19T>C variant causes a 3 prime UTR 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 (★★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 0)

Exomes 𝑓: 0.013 ( 1104 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.50

Publications

20 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

new If you want to explore the variant's impact on the transcript NM_016335.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 22-18913156-A-G is Benign according to our data. Variant chr22-18913156-A-G is described in ClinVar as Benign. ClinVar VariationId is 1298044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 1104 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016335.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRODH	NM_016335.6	MANE Select	c.*19T>C	3_prime_UTR	Exon 14 of 14	NP_057419.5
PRODH	NM_001195226.2		c.*19T>C	3_prime_UTR	Exon 14 of 14	NP_001182155.2	O43272-2
PRODH	NM_001368250.2		c.*19T>C	3_prime_UTR	Exon 14 of 14	NP_001355179.2	E7EQL6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRODH	ENST00000357068.11	TSL:1 MANE Select	c.*19T>C	3_prime_UTR	Exon 14 of 14	ENSP00000349577.6	O43272-4
PRODH	ENST00000610940.4	TSL:1	c.*19T>C	3_prime_UTR	Exon 15 of 15	ENSP00000480347.1	O43272-4
PRODH	ENST00000334029.6	TSL:1	c.*19T>C	3_prime_UTR	Exon 14 of 14	ENSP00000334726.2	O43272-2

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

AN:

22098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00202

Gnomad ASJ

AF:

0.00709

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.00160

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.933

AC:

143559

AN:

153906

AF XY:

0.932

show subpopulations

Gnomad AFR exome

AF:

0.829

Gnomad AMR exome

AF:

0.965

Gnomad ASJ exome

AF:

0.953

Gnomad EAS exome

AF:

0.960

Gnomad FIN exome

AF:

0.920

Gnomad NFE exome

AF:

0.937

Gnomad OTH exome

AF:

0.937

GnomAD4 exome

AF:

0.0131

AC:

2262

AN:

172264

Hom.:

1104

Cov.:

AF XY:

0.0144

AC XY:

1228

AN XY:

85230

show subpopulations

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

African (AFR)

AF:

0.0603

AC:

569

AN:

9434

American (AMR)

AF:

0.108

AC:

289

AN:

2678

Ashkenazi Jewish (ASJ)

AF:

0.00593

AC:

AN:

2024

East Asian (EAS)

AF:

0.0671

AC:

186

AN:

2770

South Asian (SAS)

AF:

0.0367

AC:

479

AN:

13052

European-Finnish (FIN)

AF:

0.0155

AC:

105

AN:

6788

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

784

European-Non Finnish (NFE)

AF:

0.00372

AC:

473

AN:

127220

Other (OTH)

AF:

0.0188

AC:

141

AN:

7514

⚠️ 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: 0.245

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00284

AC:

AN:

22162

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

AN XY:

10698

show subpopulations

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

African (AFR)

AF:

0.00474

AC:

AN:

10132

American (AMR)

AF:

0.00202

AC:

AN:

1486

Ashkenazi Jewish (ASJ)

AF:

0.00709

AC:

AN:

282

East Asian (EAS)

AF:

0.00270

AC:

AN:

370

South Asian (SAS)

AF:

0.00160

AC:

AN:

626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00105

AC:

AN:

7610

Other (OTH)

AF:

0.00

AC:

AN:

264

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.255

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.770

Hom.:

11817

Asia WGS

AF:

0.917

AC:

3190

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Proline dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.070

(source)

DANN

Benign

0.41

PhyloP100

-3.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over