Variant chr1-225921199-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013328.4(PYCR2):c.797+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,609,918 control chromosomes in the GnomAD database, including 9,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 637 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8377 hom. )

Consequence

PYCR2
NM_013328.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.07

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 (BayesDel_noAF=-0.85).

BP6

Variant 1-225921199-T-G is Benign according to our data. Variant chr1-225921199-T-G is described in ClinVar as [Benign]. Clinvar id is 1167877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYCR2	NM_013328.4 linkuse as main transcript	c.797+9A>C		intron_variant		ENST00000343818.11	NP_037460.2
PYCR2	NM_001271681.2 linkuse as main transcript	c.575+9A>C		intron_variant			NP_001258610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYCR2	ENST00000343818.11 linkuse as main transcript	c.797+9A>C		intron_variant		1	NM_013328.4	ENSP00000342502	P1

Frequencies

GnomAD3 genomes

AF:

0.0806

AC:

12252

AN:

152090

Hom.:

637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0192

Gnomad AMI

AF:

0.0386

Gnomad AMR

AF:

0.0714

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0597

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.100

AC:

24801

AN:

247846

Hom.:

1507

AF XY:

0.107

AC XY:

14333

AN XY:

134004

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.0474

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0586

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.0980

GnomAD4 exome

AF:

0.102

AC:

149366

AN:

1457710

Hom.:

8377

Cov.:

AF XY:

0.105

AC XY:

76380

AN XY:

725048

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.0492

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.0567

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0805

AC:

12251

AN:

152208

Hom.:

637

Cov.:

AF XY:

0.0821

AC XY:

6107

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0192

Gnomad4 AMR

AF:

0.0713

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0598

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0862

Alfa

AF:

0.0850

Hom.:

443

Bravo

AF:

0.0712

Asia WGS

AF:

0.0880

AC:

307

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.111

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2020	- -

Hypomyelinating leukodystrophy 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.60

DANN

Benign

0.53

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