Genetic Variant CNPY3:p.Leu24_Leu25del (chr6-42929619-TTGCTGC-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_006586.5(CNPY3):c.71_76delTGCTGC(p.Leu24_Leu25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,560,294 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

CNPY3
NM_006586.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.877

Variant links:

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 links:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000388 (59/151950) while in subpopulation NFE AF= 0.000692 (47/67926). AF 95% confidence interval is 0.000534. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNPY3	NM_006586.5 link	c.71_76delTGCTGC	p.Leu24_Leu25del	disruptive_inframe_deletion	Exon 1 of 6	ENST00000372836.5	NP_006577.2	Q9BT09-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNPY3	ENST00000372836.5 link	c.71_76delTGCTGC	p.Leu24_Leu25del	disruptive_inframe_deletion	Exon 1 of 6	1	NM_006586.5	ENSP00000361926.4		Q9BT09-1
ENSG00000287825	ENST00000667155.3 link	n.-146_-141delGCAGCA		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000334

AC:

AN:

128598

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

69632

show subpopulations

Gnomad AFR exome

AF:

0.000307

Gnomad AMR exome

AF:

0.0000971

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000727

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000520

AC:

733

AN:

1408344

Hom.:

AF XY:

0.000491

AC XY:

342

AN XY:

696118

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.0000545

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000497

Gnomad4 FIN exome

AF:

0.0000210

Gnomad4 NFE exome

AF:

0.000649

Gnomad4 OTH exome

AF:

0.000291

GnomAD4 genome

AF:

0.000388

AC:

AN:

151950

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000692

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

6-42929619-TTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over