chr7-155507034-C-G

Position:

• chr7-155507034-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001393663.1(CNPY1):​c.386G>C​(p.Cys129Ser) variant causes a missense change. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPY1 NM_001393663.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPY1	NM_001393663.1	c.386G>C	p.Cys129Ser	missense_variant	4/5	ENST00000636446.2	NP_001380592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNPY1	ENST00000636446.2	c.386G>C	p.Cys129Ser	missense_variant	4/5	5	NM_001393663.1	ENSP00000490477.3
ENSG00000283128	ENST00000688916.1	c.386G>C	p.Cys129Ser	missense_variant	6/7			ENSP00000510525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 06, 2021

The c.227G>C (p.C76S) alteration is located in exon 3 (coding exon 2) of the CNPY1 gene. This alteration results from a G to C substitution at nucleotide position 227, causing the cysteine (C) at amino acid position 76 to be replaced by a serine (S). 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	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T;.;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	.;T;T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.44	D
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-9.8	D;D;.;.
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D;D;.;.
Sift4G	Pathogenic	0.0	D;D;.;.
Polyphen		1.0	D;D;.;.
Vest4		0.76
MutPred		0.62		Gain of disorder (P = 0.0098);Gain of disorder (P = 0.0098);.;.;
MVP		0.51
MPC		0.42
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.95
gMVP		0.58

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: rs1014848927; hg19: chr7-155299729;