17-81932942-C-G

Variant names:

• chr17-81932942-C-G
• rs3744807
• ENST00000337943.9:c.889G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153824.3(PYCR1):​c.889G>C​(p.Gly297Arg) 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. 13/15 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 the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PYCR1 NM_153824.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

PYCR1 (HGNC:9721): (pyrroline-5-carboxylate reductase 1) This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiologic role in the generation of NADP(+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ENSG00000263585 (HGNC:56889):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07869524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYCR1	NM_006907.4	c.*272G>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000329875.13	NP_008838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYCR1	ENST00000329875	c.*272G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_006907.4	ENSP00000328858.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000408 AC: 1 AN: 245330 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133180

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: 0.00000902

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459380 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725770

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.1
DANN	Benign	0.68
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.88	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.19
Sift	Benign	0.073	T
Sift4G	Benign	0.11	T
Vest4		0.057
MutPred		0.17		Loss of glycosylation at S298 (P = 0.0963);
MVP		0.58
ClinPred		0.056	T
GERP RS		-5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3744807; hg19: chr17-79890818;