rs556172653

Variant names:

• chr6-42934598-C-A
• NM_006586.5:c.275C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-42934598-C-A
• chr6-42934598-C-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_006586.5(CNPY3):​c.275C>A​(p.Ser92*) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNPY3 NM_006586.5 stop_gained, splice_region
• Scores: Splicing: ADA: 0.8552
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04

Genes affected

CNPY3 (HGNC:11968): (canopy FGF signaling regulator 3) This gene encodes a protein that binds members of the toll-like receptor protein family and functions as a chaperone to aid in folding and export of these proteins. Alternative splicing results in multiple transcript variants. Naturally occuring readthrough transcription occurs between this locus and the downstream GNMT (glycine N-methyltransferase) gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

CNPY3-GNMT (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNPY3	NM_006586.5	c.275C>A	p.Ser92*	stop_gained, splice_region_variant	Exon 2 of 6	ENST00000372836.5	NP_006577.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNPY3	ENST00000372836.5	c.275C>A	p.Ser92*	stop_gained, splice_region_variant	Exon 2 of 6	1	NM_006586.5	ENSP00000361926.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461454 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	45
DANN	Uncertain	0.99
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
Vest4		0.51
GERP RS		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.86
dbscSNV1_RF	Pathogenic	0.80
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42902336;