chr22-18913346-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_016335.6(PRODH):c.1632C>T(p.Pro544=) 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00039 ( 4 hom., cov: 0)
Exomes 𝑓: 0.000071 ( 9 hom. )
Failed GnomAD Quality Control
Consequence
PRODH
NM_016335.6 synonymous
NM_016335.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -8.62
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 22-18913346-G-A is Benign according to our data. Variant chr22-18913346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2084915.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-8.62 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1632C>T | p.Pro544= | synonymous_variant | 14/14 | ENST00000357068.11 | |
PRODH | NM_001195226.2 | c.1308C>T | p.Pro436= | synonymous_variant | 14/14 | ||
PRODH | NM_001368250.2 | c.1308C>T | p.Pro436= | synonymous_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1632C>T | p.Pro544= | synonymous_variant | 14/14 | 1 | NM_016335.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 7AN: 25902Hom.: 3 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.0000230 AC: 4AN: 173624Hom.: 0 AF XY: 0.0000108 AC XY: 1AN XY: 92746
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000711 AC: 24AN: 337578Hom.: 9 Cov.: 0 AF XY: 0.0000589 AC XY: 10AN XY: 169882
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000385 AC: 10AN: 25972Hom.: 4 Cov.: 0 AF XY: 0.000395 AC XY: 5AN XY: 12658
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Proline dehydrogenase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
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