chr8-143605851-T-G

Position:

• chr8-143605851-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023078.6(PYCR3):​c.674A>C​(p.Gln225Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PYCR3 NM_023078.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32154524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYCR3	NM_023078.6	c.674A>C	p.Gln225Pro	missense_variant	6/6	ENST00000495276.6
PYCR3	NM_001329866.3	c.614A>C	p.Gln205Pro	missense_variant	6/6
PYCR3	NR_138144.3	n.814A>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYCR3	ENST00000495276.6	c.674A>C	p.Gln225Pro	missense_variant	6/6	1	NM_023078.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.710A>C (p.Q237P) alteration is located in exon 6 (coding exon 6) of the PYCRL gene. This alteration results from a A to C substitution at nucleotide position 710, causing the glutamine (Q) at amino acid position 237 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.065	T;T;.;D
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.74	D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	N;.;.;D
REVEL	Uncertain	0.31
Sift	Benign	0.071	T;.;.;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.31	.;B;.;.
Vest4		0.27
MutPred		0.54		.;Loss of helix (P = 0.0196);.;.;
MVP		0.79
MPC		0.39
ClinPred		0.50	T
GERP RS		2.5
Varity_R		0.20
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-144688021;