chr22-18913156-A-C

Variant names:

• chr22-18913156-A-C
• rs383964
• ENST00000482858.5:n.4302T>G

Variant summary

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

The ENST00000482858.5(PRODH):​n.4302T>G variant causes a non coding transcript exon 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: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRODH ENST00000482858.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 20 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]

ENSG00000283809 (HGNC:):

DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000482858.5. 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.*19T>G		3_prime_UTR	Exon 14 of 14	NP_057419.5
	PRODH	NM_001195226.2		c.*19T>G		3_prime_UTR	Exon 14 of 14	NP_001182155.2
	PRODH	NM_001368250.2		c.*19T>G		3_prime_UTR	Exon 14 of 14	NP_001355179.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	ENST00000482858.5	TSL:1	n.4302T>G		non_coding_transcript_exon	Exon 11 of 11
	PRODH	ENST00000491604.5	TSL:1	n.2731T>G		non_coding_transcript_exon	Exon 13 of 13
	PRODH	ENST00000357068.11	TSL:1 MANE Select	c.*19T>G		3_prime_UTR	Exon 14 of 14	ENSP00000349577.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 172930 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 85582

African (AFR) AF: 0.00 AC: 0 AN: 9660

American (AMR) AF: 0.00 AC: 0 AN: 2702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2030

East Asian (EAS) AF: 0.00 AC: 0 AN: 2802

South Asian (SAS) AF: 0.00 AC: 0 AN: 13138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 786

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 127364

Other (OTH) AF: 0.00 AC: 0 AN: 7572

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.063
DANN	Benign	0.44
PhyloP100		-3.5

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: rs383964; hg19: chr22-18900669;