chr8-143609533-G-C

Position:

• chr8-143609533-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023078.6(PYCR3):​c.16C>G​(p.Pro6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,359,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PYCR3 NM_023078.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

Genes affected

PYCR3 (HGNC:25846): (pyrroline-5-carboxylate reductase 3) This gene encodes a protein that belongs to the pyrroline-5-carboxylate reductase family of enzymes. Members of this family catalyze the final step in proline biosynthesis, converting pyrroline-5-carboxylate to proline. Glutamate and ornithine are precursors in the synthesis of proline. The protein encoded by this gene is a cytoplasmic enzyme involved in the biosynthesis of proline from ornithine. [provided by RefSeq, Aug 2016]

PYCR3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0430564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYCR3	NM_023078.6	c.16C>G	p.Pro6Ala	missense_variant	1/6	ENST00000495276.6	NP_075566.3
PYCR3	NM_001329866.3	c.16C>G	p.Pro6Ala	missense_variant	1/6		NP_001316795.2
PYCR3	NR_138144.3	n.43C>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYCR3	ENST00000495276.6	c.16C>G	p.Pro6Ala	missense_variant	1/6	1	NM_023078.6	ENSP00000480945.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000944 AC: 1 AN: 105896 Hom.: 0 AF XY: 0.0000168 AC XY: 1 AN XY: 59564

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000251

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1359118 Hom.: 0 Cov.: 32 AF XY: 0.00000298 AC XY: 2 AN XY: 670986

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.050
DANN	Benign	0.44
DEOGEN2	Benign	0.0024	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.053	N
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.57	.;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.46	N;.;.
REVEL	Benign	0.082
Sift	Benign	0.47	T;.;.
Sift4G	Benign	0.83	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.068
MutPred		0.26		.;Loss of glycosylation at P6 (P = 0.0148);Loss of glycosylation at P6 (P = 0.0148);
MVP		0.12
MPC		0.20
ClinPred		0.065	T
GERP RS		-5.0
Varity_R		0.021
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs193920765; hg19: chr8-144691703;