1-225921194-C-T

Variant names:

• chr1-225921194-C-T
• rs10915897
• NM_013328.4:c.797+14G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013328.4(PYCR2):​c.797+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,606,882 control chromosomes in the GnomAD database, including 21,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2485 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18814 hom.)
• Consequence: PYCR2 NM_013328.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.15

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]

ENSG00000255835 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-225921194-C-T is Benign according to our data. Variant chr1-225921194-C-T is described in ClinVar as [Benign]. Clinvar id is 1166899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYCR2	NM_013328.4	c.797+14G>A		intron_variant	Intron 6 of 6	ENST00000343818.11	NP_037460.2
PYCR2	NM_001271681.2	c.575+14G>A		intron_variant	Intron 5 of 5		NP_001258610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYCR2	ENST00000343818.11	c.797+14G>A		intron_variant	Intron 6 of 6	1	NM_013328.4	ENSP00000342502.6
ENSG00000255835	ENST00000432920.2	c.575+14G>A		intron_variant	Intron 5 of 7	2		ENSP00000414068.2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26542 AN: 151954 Hom.: 2472 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.193 AC: 47346 AN: 245590 AF XY: 0.192

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.341

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.152 AC: 221528 AN: 1454812 Hom.: 18814 Cov.: 32 AF XY: 0.155 AC XY: 112308 AN XY: 723488

African (AFR) AF: 0.197 AC: 6564 AN: 33308

American (AMR) AF: 0.250 AC: 10969 AN: 43952

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5057 AN: 25628

East Asian (EAS) AF: 0.341 AC: 13529 AN: 39650

South Asian (SAS) AF: 0.236 AC: 20148 AN: 85414

European-Finnish (FIN) AF: 0.172 AC: 9150 AN: 53220

Middle Eastern (MID) AF: 0.184 AC: 1051 AN: 5706

European-Non Finnish (NFE) AF: 0.131 AC: 145181 AN: 1107866

Other (OTH) AF: 0.164 AC: 9879 AN: 60068

GnomAD4 genome AF: 0.175 AC: 26589 AN: 152070 Hom.: 2485 Cov.: 32 AF XY: 0.179 AC XY: 13279 AN XY: 74316

African (AFR) AF: 0.196 AC: 8119 AN: 41458

American (AMR) AF: 0.225 AC: 3441 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1750 AN: 5164

South Asian (SAS) AF: 0.232 AC: 1121 AN: 4824

European-Finnish (FIN) AF: 0.167 AC: 1766 AN: 10572

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9201 AN: 67980

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.151 Hom.: 1665

Bravo AF: 0.178

Asia WGS AF: 0.306 AC: 1061 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypomyelinating leukodystrophy 10 Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.35
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs10915897; hg19: chr1-226108894; COSMIC: COSV59524689; COSMIC: COSV59524689;