rs13058335

Variant names:

• chr22-18922966-C-T
• rs13058335
• ENST00000482858.5:n.736G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000482858.5(PRODH):​n.736G>A 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. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRODH ENST00000482858.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.09
• 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: Benign. The variant received -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 VariationId is 1247033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.733-33G>A		intron	N/A	NP_057419.5
	PRODH	NM_001195226.2		c.409-33G>A		intron	N/A	NP_001182155.2
	PRODH	NM_001368250.2		c.409-33G>A		intron	N/A	NP_001355179.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	ENST00000482858.5	TSL:1	n.736G>A		non_coding_transcript_exon	Exon 5 of 11
	PRODH	ENST00000357068.11	TSL:1 MANE Select	c.733-33G>A		intron	N/A	ENSP00000349577.6
	PRODH	ENST00000610940.4	TSL:1	c.733-33G>A		intron	N/A	ENSP00000480347.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0493 AC: 12375 AN: 251226 AF XY: 0.0499

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 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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.59
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13058335; hg19: chr22-18910479; COSMIC: COSV58230253; COSMIC: COSV58230253;