Variant 1-225920500-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013328.4(PYCR2):c.918G>A(p.Gly306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,512,040 control chromosomes in the GnomAD database, including 22,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3368 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18640 hom. )

Consequence

PYCR2
NM_013328.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.162

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 1-225920500-C-T is Benign according to our data. Variant chr1-225920500-C-T is described in ClinVar as [Benign]. Clinvar id is 1166246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.162 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 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.918G>A	p.Gly306=	synonymous_variant	7/7	ENST00000343818.11	NP_037460.2
PYCR2	NM_001271681.2 linkuse as main transcript	c.696G>A	p.Gly232=	synonymous_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.918G>A	p.Gly306=	synonymous_variant	7/7	1	NM_013328.4	ENSP00000342502	P1
PYCR2	ENST00000612039.4 linkuse as main transcript	c.696G>A	p.Gly232=	synonymous_variant	6/6	3		ENSP00000478165
PYCR2	ENST00000478402.5 linkuse as main transcript	n.2527G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30068

AN:

151838

Hom.:

3368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0810

Gnomad SAS

AF:

0.0630

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.174

AC:

38600

AN:

222218

Hom.:

4116

AF XY:

0.163

AC XY:

19625

AN XY:

120260

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0914

Gnomad SAS exome

AF:

0.0654

Gnomad FIN exome

AF:

0.209

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.158

AC:

215469

AN:

1360082

Hom.:

18640

Cov.:

AF XY:

0.154

AC XY:

104642

AN XY:

678536

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.306

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0771

Gnomad4 SAS exome

AF:

0.0674

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.198

AC:

30095

AN:

151958

Hom.:

3368

Cov.:

AF XY:

0.197

AC XY:

14648

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0808

Gnomad4 SAS

AF:

0.0632

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.171

Hom.:

953

Bravo

AF:

0.208

Asia WGS

AF:

0.0750

AC:

263

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.2

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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