rs2016118

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-18928303-T-A
• chr22-18928303-T-C

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>T 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 0.0 (0 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=-0.89).

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 116954 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 116954 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 56102

African (AFR) AF: 0.00 AC: 0 AN: 37572

American (AMR) AF: 0.00 AC: 0 AN: 11400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2826

East Asian (EAS) AF: 0.00 AC: 0 AN: 4834

South Asian (SAS) AF: 0.00 AC: 0 AN: 3610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 48292

Other (OTH) AF: 0.00 AC: 0 AN: 1584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.79

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;