22-18928303-T-C

Variant names:

• chr22-18928303-T-C
• rs2016118
• NM_016335.6:c.483-2581A>G

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine, Orphanet

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: 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.483-2581A>G		intron	N/A	NP_057419.5
	PRODH	NM_001195226.2		c.159-2581A>G		intron	N/A	NP_001182155.2	O43272-2
	PRODH	NM_001368250.2		c.159-2581A>G		intron	N/A	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.483-2581A>G		intron	N/A	ENSP00000349577.6	O43272-4
	PRODH	ENST00000610940.4	TSL:1	c.483-2581A>G		intron	N/A	ENSP00000480347.1	O43272-4
	PRODH	ENST00000334029.6	TSL:1	c.159-2581A>G		intron	N/A	ENSP00000334726.2	O43272-2

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

African (AFR) AF: 0.971 AC: 36595 AN: 37682

American (AMR) AF: 0.929 AC: 10605 AN: 11416

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 2710 AN: 2826

East Asian (EAS) AF: 0.951 AC: 4576 AN: 4814

South Asian (SAS) AF: 0.917 AC: 3306 AN: 3604

European-Finnish (FIN) AF: 0.851 AC: 5058 AN: 5944

Middle Eastern (MID) AF: 0.898 AC: 185 AN: 206

European-Non Finnish (NFE) AF: 0.914 AC: 44139 AN: 48272

Other (OTH) AF: 0.942 AC: 1516 AN: 1610

Alfa AF: 0.806 Hom.: 6203

Asia WGS AF: 0.834 AC: 2900 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	1.8
DANN	Benign	0.44
PhyloP100		-0.79
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: rs2016118; hg19: chr22-18915816;