22-18925165-A-T

Position:

• chr22-18925165-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000357068.11(PRODH):​c.553T>A​(p.Trp185Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W185Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRODH ENST00000357068.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08179915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRODH	NM_016335.6	c.553T>A	p.Trp185Arg	missense_variant	4/14	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2	c.229T>A	p.Trp77Arg	missense_variant	4/14		NP_001182155.2
PRODH	NM_001368250.2	c.229T>A	p.Trp77Arg	missense_variant	4/14		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11	c.553T>A	p.Trp185Arg	missense_variant	4/14	1	NM_016335.6	ENSP00000349577	P3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.2
DANN	Benign	0.24
DEOGEN2	Benign	0.0026	T;.;.;T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.91
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.0069	T;.;T;.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.082	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	3.7	.;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.50	.;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T
Polyphen		0.0	.;B;B;.;.
Vest4		0.033
MutPred		0.32		.;Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);.;.;
MVP		0.35
MPC		0.48
ClinPred		0.067	T
GERP RS		2.9
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs4819756; hg19: chr22-18912678;