chr22-18933003-C-T

Variant names:

• chr22-18933003-C-T
• rs4819757
• NM_016335.6:c.274-1805G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000357068.11(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 ENST00000357068.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 4 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: ClinGen, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000283809 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357068.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	NM_016335.6	MANE Select	c.274-1805G>A		intron	N/A	NP_057419.5
	PRODH	NM_001195226.2		c.-51-1805G>A		intron	N/A	NP_001182155.2
	PRODH	NM_001368250.2		c.-51-1805G>A		intron	N/A	NP_001355179.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	ENST00000357068.11	TSL:1 MANE Select	c.274-1805G>A		intron	N/A	ENSP00000349577.6
	PRODH	ENST00000610940.4	TSL:1	c.274-1805G>A		intron	N/A	ENSP00000480347.1
	PRODH	ENST00000334029.6	TSL:1	c.-51-1805G>A		intron	N/A	ENSP00000334726.2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 295 AN: 472 Hom.: 108 Cov.: 0

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

African (AFR) AF: 0.875 AC: 70 AN: 80

American (AMR) AF: 0.541 AC: 40 AN: 74

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 7 AN: 8

East Asian (EAS) AF: 0.926 AC: 50 AN: 54

South Asian (SAS) AF: 0.737 AC: 28 AN: 38

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.448 AC: 87 AN: 194

Other (OTH) AF: 0.625 AC: 15 AN: 24

Alfa AF: 0.630 Hom.: 3973

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.83
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4819757; hg19: chr22-18920516;