rs4269009

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016335.6(PRODH):​c.668-152T>C 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
NM_016335.6 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.15
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 22-18923331-A-G is Benign according to our data. Variant chr22-18923331-A-G is described in ClinVar as [Benign]. Clinvar id is 1285790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRODHNM_016335.6 linkc.668-152T>C intron_variant Intron 4 of 13 ENST00000357068.11 NP_057419.5 O43272
PRODHNM_001195226.2 linkc.344-152T>C intron_variant Intron 4 of 13 NP_001182155.2 O43272
PRODHNM_001368250.2 linkc.344-152T>C intron_variant Intron 4 of 13 NP_001355179.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRODHENST00000357068.11 linkc.668-152T>C intron_variant Intron 4 of 13 1 NM_016335.6 ENSP00000349577.6 O43272
ENSG00000283809ENST00000638240.1 linkc.513+12303A>G intron_variant Intron 4 of 5 5 ENSP00000492446.1 A0A1W2PRQ8

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
0
Alfa
AF:
0.0229
Hom.:
3
Asia WGS
AF:
0.0900
AC:
313
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 19, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.090
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4269009; hg19: chr22-18910844; COSMIC: COSV58231029; COSMIC: COSV58231029; API