6-42934564-G-T

Position:

• chr6-42934564-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006586.5(CNPY3):​c.241G>T​(p.Asp81Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D81E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPY3 NM_006586.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNPY3	NM_006586.5	c.241G>T	p.Asp81Tyr	missense_variant	2/6	ENST00000372836.5
CNPY3-GNMT	NR_134890.2	n.243-1010G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNPY3	ENST00000372836.5	c.241G>T	p.Asp81Tyr	missense_variant	2/6	1	NM_006586.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 60 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Aug 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.68	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.74
MutPred		0.60		Loss of ubiquitination at K83 (P = 0.051);Loss of ubiquitination at K83 (P = 0.051);
MVP		0.49
MPC		0.71
ClinPred		1.0	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-42902302;