17-81932942-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153824.3(PYCR1):c.889G>A(p.Gly297Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,611,660 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.010 ( 28 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 201 hom. )

Consequence

PYCR1
NM_153824.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.10

Variant links:

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]

PYCR1 links:

ENSG00000263585 (HGNC:56889):

ENSG00000263585 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018904805).

BP6

Variant 17-81932942-C-T is Benign according to our data. Variant chr17-81932942-C-T is described in ClinVar as [Benign]. Clinvar id is 325898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYCR1	NM_006907.4 link	c.*272G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000329875.13	NP_008838.2	P32322-1A0A024R8U9Q8TBX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYCR1	ENST00000329875 link	c.*272G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_006907.4	ENSP00000328858.8		P32322-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1536

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0556

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0302

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0151

AC:

3694

AN:

245330

Hom.:

146

AF XY:

0.0117

AC XY:

1554

AN XY:

133180

show subpopulations

Gnomad AFR exome

AF:

0.00998

Gnomad AMR exome

AF:

0.0806

Gnomad ASJ exome

AF:

0.000608

Gnomad EAS exome

AF:

0.0321

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.000824

Gnomad NFE exome

AF:

0.000559

Gnomad OTH exome

AF:

0.00884

GnomAD4 exome

AF:

0.00426

AC:

6216

AN:

1459336

Hom.:

201

Cov.:

AF XY:

0.00379

AC XY:

2753

AN XY:

725750

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0752

Gnomad4 ASJ exome

AF:

0.000614

Gnomad4 EAS exome

AF:

0.0446

Gnomad4 SAS exome

AF:

0.00252

Gnomad4 FIN exome

AF:

0.000974

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.0101

AC:

1539

AN:

152324

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

838

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.0556

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0299

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00300

Hom.:

Bravo

AF:

0.0146

ESP6500AA

AF:

0.00773

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0121

AC:

1469

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cutis laxa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.0

DANN

Benign

0.70

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.94

PROVEAN

Benign

0.19

REVEL

Benign

0.17

Sift

Benign

0.073

Sift4G

Benign

0.11

Vest4

0.057

MutPred

0.17

Loss of glycosylation at S298 (P = 0.0963);

ClinPred

0.0029

GERP RS

-5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over