17-81933064-G-T

Variant names:

• chr17-81933064-G-T
• rs968788815
• NM_006907.4:c.*150C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006907.4(PYCR1):​c.*150C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,427,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PYCR1 NM_006907.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.*150C>A		3_prime_UTR	Exon 7 of 7	NP_008838.2
	PYCR1	NM_001282281.2		c.*150C>A		3_prime_UTR	Exon 8 of 8	NP_001269210.1	P32322-3
	PYCR1	NM_001282280.2		c.*150C>A		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.*150C>A		3_prime_UTR	Exon 7 of 7	ENSP00000328858.8	P32322-1
	PYCR1	ENST00000619204.4	TSL:1	c.*150C>A		3_prime_UTR	Exon 8 of 8	ENSP00000479793.1	P32322-1
	PYCR1	ENST00000403172.8	TSL:1	c.*150C>A		3_prime_UTR	Exon 7 of 7	ENSP00000385483.4	E2QRB3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427894 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 708734

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32872

American (AMR) AF: 0.00 AC: 0 AN: 40184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 38302

South Asian (SAS) AF: 0.00 AC: 0 AN: 83264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100680

Other (OTH) AF: 0.00 AC: 0 AN: 59514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.68
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs968788815; hg19: chr17-79890940;