chr7-155509019-C-G

Position:

• chr7-155509019-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393663.1(CNPY1):​c.178G>C​(p.Glu60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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)
• Consequence: CNPY1 NM_001393663.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

CNPY1 (HGNC:27786): (canopy FGF signaling regulator 1) Cnpy1 is expressed in the midbrain-hindbrain (MHB) boundary in zebrafish, binds FGFR1 (MIM 136350), and plays a role in FGF signaling (Hirate and Okamoto, 2006 [PubMed 16488878]).[supplied by OMIM, Dec 2008]

ENSG00000283128 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08272362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPY1	NM_001393663.1	c.178G>C	p.Glu60Gln	missense_variant	3/5	ENST00000636446.2	NP_001380592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNPY1	ENST00000636446.2	c.178G>C	p.Glu60Gln	missense_variant	3/5	5	NM_001393663.1	ENSP00000490477.3
ENSG00000283128	ENST00000688916.1	c.178G>C	p.Glu60Gln	missense_variant	5/7			ENSP00000510525.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.19G>C (p.E7Q) alteration is located in exon 2 (coding exon 1) of the CNPY1 gene. This alteration results from a G to C substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.75
DEOGEN2	Benign	0.0072	T;T;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.73	.;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.47	N;N;.;.
REVEL	Benign	0.028
Sift	Benign	0.49	T;T;.;.
Sift4G	Benign	0.55	T;T;.;.
Polyphen		0.032	B;B;.;.
Vest4		0.086
MutPred		0.20		Gain of methylation at K5 (P = 0.106);Gain of methylation at K5 (P = 0.106);.;.;
MVP		0.014
MPC		0.067
ClinPred		0.70	D
GERP RS		3.1
Varity_R		0.10
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs1796428577; hg19: chr7-155301714;