dbSNP rs1076466: PRODH:c.1105-14C>T (chr22-18919611-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016335.6(PRODH):c.1105-14C>T variant causes a intron 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 0.60 ( 56 hom., cov: 0)

Exomes 𝑓: 0.66 ( 3495 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.299

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 22-18919611-G-A is Benign according to our data. Variant chr22-18919611-G-A is described in ClinVar as [Benign]. Clinvar id is 1169512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18919611-G-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRODH	NM_016335.6 link	c.1105-14C>T	intron_variant	Intron 9 of 13	ENST00000357068.11	NP_057419.5	O43272
PRODH	NM_001195226.2 link	c.781-14C>T	intron_variant	Intron 9 of 13		NP_001182155.2	O43272
PRODH	NM_001368250.2 link	c.781-14C>T	intron_variant	Intron 9 of 13		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11 link	c.1105-14C>T		intron_variant	Intron 9 of 13	1	NM_016335.6	ENSP00000349577.6		O43272
ENSG00000283809	ENST00000638240.1 link	c.513+8583G>A		intron_variant	Intron 4 of 5	5		ENSP00000492446.1		A0A1W2PRQ8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

150

AN:

250

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.517

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.750

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.667

GnomAD3 exomes

AF:

0.457

AC:

109476

AN:

239750

Hom.:

25925

AF XY:

0.464

AC XY:

60226

AN XY:

129864

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.410

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.748

Gnomad SAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.664

AC:

9927

AN:

14960

Hom.:

3495

Cov.:

AF XY:

0.669

AC XY:

5417

AN XY:

8094

show subpopulations

Gnomad4 AFR exome

AF:

0.592

Gnomad4 AMR exome

AF:

0.593

Gnomad4 ASJ exome

AF:

0.660

Gnomad4 EAS exome

AF:

0.898

Gnomad4 SAS exome

AF:

0.775

Gnomad4 FIN exome

AF:

0.597

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.628

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.603

AC:

152

AN:

252

Hom.:

Cov.:

AF XY:

0.591

AC XY:

AN XY:

110

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.376

Hom.:

1398

Asia WGS

AF:

0.633

AC:

2199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Proline dehydrogenase deficiency

Benign:2

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.1

DANN

Benign

0.85

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