22-18933003-C-T

Position:

• chr22-18933003-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016335.6(PRODH):​c.274-1805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (112 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: PRODH NM_016335.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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]

ENSG00000283809 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRODH	NM_016335.6	c.274-1805G>A		intron_variant		ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2	c.-51-1805G>A		intron_variant			NP_001182155.2
PRODH	NM_001368250.2	c.-51-1805G>A		intron_variant			NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11	c.274-1805G>A		intron_variant		1	NM_016335.6	ENSP00000349577.6
ENSG00000283809	ENST00000638240.1	c.514-6670C>T		intron_variant		5		ENSP00000492446.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 295 AN: 472 Hom.: 108 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.886

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.628 AC: 300 AN: 478 Hom.: 112 Cov.: 0 AF XY: 0.617 AC XY: 153 AN XY: 248

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.625

Alfa AF: 0.630 Hom.: 3973

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs4819757; hg19: chr22-18920516;