NM_016335.6:c.80G>A

Variant names:

• chr22-18936208-C-T
• rs1411529753
• NM_016335.6:c.80G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016335.6(PRODH):​c.80G>A​(p.Arg27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R27L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRODH NM_016335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.107798845).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016335.6. 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.80G>A	p.Arg27His	missense	Exon 1 of 14	NP_057419.5
	PRODH	NM_001368250.2		c.-90G>A		5_prime_UTR	Exon 1 of 14	NP_001355179.2
	PRODH	NM_001195226.2		c.-52+182G>A		intron	N/A	NP_001182155.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRODH	ENST00000357068.11	TSL:1 MANE Select	c.80G>A	p.Arg27His	missense	Exon 1 of 14	ENSP00000349577.6
	PRODH	ENST00000610940.4	TSL:1	c.80G>A	p.Arg27His	missense	Exon 2 of 15	ENSP00000480347.1
	PRODH	ENST00000491604.5	TSL:1	n.88G>A		non_coding_transcript_exon	Exon 1 of 13

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.052
Sift	Benign	0.12	T
Sift4G	Benign	0.15	T
Vest4		0.10
MutPred		0.22		Loss of solvent accessibility (P = 0.0907)
MVP		0.030
MPC		0.85
ClinPred		0.90	D
GERP RS		-1.1
PromoterAI		-0.0041	Neutral
gMVP		0.48
Mutation Taster		=96/4	polymorphism

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: rs1411529753; hg19: chr22-18923721;