PRODH p.Ala454Ala

Variant names:

• chr22-18918380-C-C
• NM_016335.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr22-18918381--
• chr22-18918381-C-A
• chr22-18918381-C-G
• chr22-18918381-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016335.6(PRODH):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 4)
• Consequence: PRODH NM_016335.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.07
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hyperprolinemia type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen

ENSG00000283809 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	NM_016335.6	MANE Select	c.		exon_region	Exon 11 of 14	NP_057419.5
	PRODH	NM_001195226.2		c.		exon_region	Exon 11 of 14	NP_001182155.2	O43272-2
	PRODH	NM_001368250.2		c.		exon_region	Exon 11 of 14	NP_001355179.2	E7EQL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	ENST00000357068.11	TSL:1 MANE Select	c.		exon_region	Exon 11 of 14	ENSP00000349577.6	O43272-4
	PRODH	ENST00000610940.4	TSL:1	c.		exon_region	Exon 12 of 15	ENSP00000480347.1	O43272-4
	PRODH	ENST00000334029.6	TSL:1	c.		exon_region	Exon 11 of 14	ENSP00000334726.2	O43272-2

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-7.1

Splicing

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.

Other links and lift over

hg19: chr22-18905893;