rs13058335

Positions:

• chr22-18922966-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000357068.11(PRODH):​c.733-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRODH ENST00000357068.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-18922966-C-T is Benign according to our data. Variant chr22-18922966-C-T is described in ClinVar as [Benign]. Clinvar id is 1247033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRODH	NM_016335.6	c.733-33G>A		intron_variant		ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2	c.409-33G>A		intron_variant			NP_001182155.2
PRODH	NM_001368250.2	c.409-33G>A		intron_variant			NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11	c.733-33G>A		intron_variant		1	NM_016335.6	ENSP00000349577	P3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0493 AC: 12375 AN: 251226 Hom.: 440 AF XY: 0.0499 AC XY: 6773 AN XY: 135840

Gnomad AFR exome AF: 0.0216

Gnomad AMR exome AF: 0.0290

Gnomad ASJ exome AF: 0.0329

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0141

Gnomad FIN exome AF: 0.0387

Gnomad NFE exome AF: 0.0798

Gnomad OTH exome AF: 0.0569

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.0502 Hom.: 27

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs13058335; hg19: chr22-18910479; COSMIC: COSV58230253; COSMIC: COSV58230253;