Variant 1-225920477-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013328.4(PYCR2):c.941C>G(p.Ala314Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00063 in 1,467,138 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00080 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00061 ( 8 hom. )

Consequence

PYCR2
NM_013328.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.492

Variant links:

Genes affected

PYCR2 (HGNC:30262): (pyrroline-5-carboxylate reductase 2) This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

PYCR2 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=0.0033650994).

BP6

Variant 1-225920477-G-C is Benign according to our data. Variant chr1-225920477-G-C is described in ClinVar as [Benign]. Clinvar id is 730211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000802 (122/152212) while in subpopulation EAS AF= 0.0226 (117/5176). AF 95% confidence interval is 0.0193. There are 2 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYCR2	NM_013328.4 linkuse as main transcript	c.941C>G	p.Ala314Gly	missense_variant	7/7	ENST00000343818.11	NP_037460.2
PYCR2	NM_001271681.2 linkuse as main transcript	c.719C>G	p.Ala240Gly	missense_variant	6/6		NP_001258610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PYCR2	ENST00000343818.11 linkuse as main transcript	c.941C>G	p.Ala314Gly	missense_variant	7/7	1	NM_013328.4	ENSP00000342502	P1
PYCR2	ENST00000612039.4 linkuse as main transcript	c.719C>G	p.Ala240Gly	missense_variant	6/6	3		ENSP00000478165
PYCR2	ENST00000478402.5 linkuse as main transcript	n.2550C>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

122

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0226

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00179

AC:

353

AN:

197250

Hom.:

AF XY:

0.00174

AC XY:

184

AN XY:

105714

show subpopulations

Gnomad AFR exome

AF:

0.0000668

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000441

GnomAD4 exome

AF:

0.000610

AC:

802

AN:

1314926

Hom.:

Cov.:

AF XY:

0.000600

AC XY:

392

AN XY:

653484

show subpopulations

Gnomad4 AFR exome

AF:

0.000140

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0195

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000298

Gnomad4 OTH exome

AF:

0.000946

GnomAD4 genome

AF:

0.000802

AC:

122

AN:

152212

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000601

Hom.:

Bravo

AF:

0.00101

ExAC

AF:

0.00149

AC:

181

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 12, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.3

DANN

Benign

0.93

DEOGEN2

Benign

0.0063

T;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.9

.;.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.17

.;.;N

REVEL

Benign

0.18

Sift

Uncertain

0.023

.;.;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.55

.;.;P

Vest4

0.069

MVP

0.89

MPC

0.30

ClinPred

0.018

GERP RS

-0.23

Varity_R

0.029

gMVP

0.16

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