22-18928303-T-C

Position:

• chr22-18928303-T-C

Variant summary

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

The NM_016335.6(PRODH):​c.483-2581A>G 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 0.93 (52473 hom., cov: 16)
  • Failed GnomAD Quality Control
• Consequence: PRODH NM_016335.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789

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.483-2581A>G		intron_variant		ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2	c.159-2581A>G		intron_variant			NP_001182155.2
PRODH	NM_001368250.2	c.159-2581A>G		intron_variant			NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11	c.483-2581A>G		intron_variant		1	NM_016335.6	ENSP00000349577.6
ENSG00000283809	ENST00000638240.1	c.514-11370T>C		intron_variant		5		ENSP00000492446.1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 109176 AN: 116910 Hom.: 52420 Cov.: 16

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.946

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: 0.934 AC: 109295 AN: 117040 Hom.: 52473 Cov.: 16 AF XY: 0.933 AC XY: 52411 AN XY: 56204

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.942

Alfa AF: 0.800 Hom.: 5875

Asia WGS AF: 0.834 AC: 2900 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	1.8
DANN	Benign	0.44

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: rs2016118; hg19: chr22-18915816;