chr22-18928450-G-T

Variant names:

• chr22-18928450-G-T
• rs2016108
• NM_016335.6:c.482+2540C>A

Variant summary

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

The NM_016335.6(PRODH):​c.482+2540C>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 0.000087 (0 hom., cov: 5)
  • Failed GnomAD Quality Control
• Consequence: PRODH NM_016335.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 7 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: NM_016335.6. 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.482+2540C>A		intron	N/A	NP_057419.5
	PRODH	NM_001195226.2		c.158+2540C>A		intron	N/A	NP_001182155.2
	PRODH	NM_001368250.2		c.158+2540C>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.482+2540C>A		intron	N/A	ENSP00000349577.6
	PRODH	ENST00000610940.4	TSL:1	c.482+2540C>A		intron	N/A	ENSP00000480347.1
	PRODH	ENST00000334029.6	TSL:1	c.158+2540C>A		intron	N/A	ENSP00000334726.2

Frequencies

GnomAD3 genomes AF: 0.0000872 AC: 2 AN: 22932 Hom.: 0 Cov.: 5

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: 0.000206

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: AS_VQSR AF: 0.0000872 AC: 2 AN: 22932 Hom.: 0 Cov.: 5 AF XY: 0.0000944 AC XY: 1 AN XY: 10588

African (AFR) AF: 0.00 AC: 0 AN: 7498

American (AMR) AF: 0.00 AC: 0 AN: 2136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 666

East Asian (EAS) AF: 0.00 AC: 0 AN: 1016

South Asian (SAS) AF: 0.00 AC: 0 AN: 412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.000206 AC: 2 AN: 9700

Other (OTH) AF: 0.00 AC: 0 AN: 262

Alfa AF: 0.00 Hom.: 8568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.43
DANN	Benign	0.56
PhyloP100		-0.75

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: rs2016108; hg19: chr22-18915963;