chr22-18913355-G-C
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_016335.6(PRODH):c.1623C>G(p.Ala541=) variant causes a synonymous 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A541A) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Failed GnomAD Quality Control
Consequence
PRODH
NM_016335.6 synonymous
NM_016335.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.85
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 22-18913355-G-C is Benign according to our data. Variant chr22-18913355-G-C is described in ClinVar as [Benign]. Clinvar id is 459913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.85 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1623C>G | p.Ala541= | synonymous_variant | 14/14 | ENST00000357068.11 | |
PRODH | NM_001195226.2 | c.1299C>G | p.Ala433= | synonymous_variant | 14/14 | ||
PRODH | NM_001368250.2 | c.1299C>G | p.Ala433= | synonymous_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1623C>G | p.Ala541= | synonymous_variant | 14/14 | 1 | NM_016335.6 | P3 |
Frequencies
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GnomAD3 exomes AF: 0.00220 AC: 381AN: 173232Hom.: 8 AF XY: 0.00147 AC XY: 136AN XY: 92430
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 23910Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 11552
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Proline dehydrogenase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Proline dehydrogenase deficiency;C1833247:Schizophrenia 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 26, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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