chr22-18913237-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_016335.6(PRODH):c.1741C>T(p.Leu581=) variant causes a synonymous change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.000032 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000016 ( 3 hom. )
Failed GnomAD Quality Control
Consequence
PRODH
NM_016335.6 synonymous
NM_016335.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 6.17
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 22-18913237-G-A is Benign according to our data. Variant chr22-18913237-G-A is described in ClinVar as [Benign]. Clinvar id is 127267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18913237-G-A is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1741C>T | p.Leu581= | synonymous_variant | 14/14 | ENST00000357068.11 | |
PRODH | NM_001195226.2 | c.1417C>T | p.Leu473= | synonymous_variant | 14/14 | ||
PRODH | NM_001368250.2 | c.1417C>T | p.Leu473= | synonymous_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1741C>T | p.Leu581= | synonymous_variant | 14/14 | 1 | NM_016335.6 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 31630Hom.: 0 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.783 AC: 125626AN: 160360Hom.: 49346 AF XY: 0.789 AC XY: 66993AN XY: 84882
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000158 AC: 8AN: 505186Hom.: 3 Cov.: 0 AF XY: 0.0000281 AC XY: 7AN XY: 248788
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000315 AC: 1AN: 31716Hom.: 0 Cov.: 0 AF XY: 0.0000650 AC XY: 1AN XY: 15382
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
Proline dehydrogenase deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at