NM_006907.4:c.*352C>G

Variant names:

• chr17-81932862-G-C
• rs149456432
• NM_006907.4:c.*352C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006907.4(PYCR1):​c.*352C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,602,872 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: PYCR1 NM_006907.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.415
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive cutis laxa type 2B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• PYCR1-related de Barsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics
• geroderma osteodysplastica

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PYCR1-AS1 (HGNC:56889):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0014 (214/152362) while in subpopulation NFE AF = 0.00248 (169/68038). AF 95% confidence interval is 0.00218. There are 2 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYCR1	NM_006907.4	MANE Select	c.*352C>G		3_prime_UTR	Exon 7 of 7	NP_008838.2
	PYCR1	NM_001282281.2		c.*352C>G		3_prime_UTR	Exon 8 of 8	NP_001269210.1	P32322-3
	PYCR1	NM_001282280.2		c.*352C>G		3_prime_UTR	Exon 8 of 8	NP_001269209.1	P32322-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYCR1	ENST00000329875.13	TSL:1 MANE Select	c.*352C>G		3_prime_UTR	Exon 7 of 7	ENSP00000328858.8	P32322-1
	PYCR1	ENST00000619204.4	TSL:1	c.*352C>G		3_prime_UTR	Exon 8 of 8	ENSP00000479793.1	P32322-1
	PYCR1	ENST00000337943.9	TSL:1	c.*18C>G		3_prime_UTR	Exon 8 of 8	ENSP00000336579.5	P32322-2

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152244 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000898 AC: 208 AN: 231652 AF XY: 0.000868

Gnomad AFR exome AF: 0.000210

Gnomad AMR exome AF: 0.000273

Gnomad ASJ exome AF: 0.000419

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000985

Gnomad NFE exome AF: 0.00159

Gnomad OTH exome AF: 0.000696

GnomAD4 exome AF: 0.00161 AC: 2333 AN: 1450510 Hom.: 2 Cov.: 30 AF XY: 0.00157 AC XY: 1129 AN XY: 720538

African (AFR) AF: 0.000360 AC: 12 AN: 33316

American (AMR) AF: 0.000276 AC: 12 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 8 AN: 25822

East Asian (EAS) AF: 0.00 AC: 0 AN: 39372

South Asian (SAS) AF: 0.0000710 AC: 6 AN: 84486

European-Finnish (FIN) AF: 0.000842 AC: 43 AN: 51056

Middle Eastern (MID) AF: 0.000358 AC: 2 AN: 5584

European-Non Finnish (NFE) AF: 0.00197 AC: 2177 AN: 1107434

Other (OTH) AF: 0.00122 AC: 73 AN: 60014

GnomAD4 genome AF: 0.00140 AC: 214 AN: 152362 Hom.: 2 Cov.: 33 AF XY: 0.00121 AC XY: 90 AN XY: 74504

African (AFR) AF: 0.000433 AC: 18 AN: 41584

American (AMR) AF: 0.000523 AC: 8 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00248 AC: 169 AN: 68038

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00158 Hom.: 1

Bravo AF: 0.00111

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cutis laxa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149456432; hg19: chr17-79890738;