1-175004777-C-G

Position:

• chr1-175004777-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014412.3(CACYBP):​c.179C>G​(p.Pro60Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CACYBP NM_014412.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

Genes affected

CACYBP (HGNC:30423): (calcyclin binding protein) The protein encoded by this gene is a calcyclin binding protein. It may be involved in calcium-dependent ubiquitination and subsequent proteosomal degradation of target proteins. It probably serves as a molecular bridge in ubiquitin E3 complexes and participates in the ubiquitin-mediated degradation of beta-catenin. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28255093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACYBP	NM_014412.3	c.179C>G	p.Pro60Arg	missense_variant	2/6	ENST00000367679.7	NP_055227.1
CACYBP	NM_001007214.1	c.50C>G	p.Pro17Arg	missense_variant	2/6		NP_001007215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACYBP	ENST00000367679.7	c.179C>G	p.Pro60Arg	missense_variant	2/6	1	NM_014412.3	ENSP00000356652	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Nov 08, 2022

The c.179C>G (p.P60R) alteration is located in exon 2 (coding exon 2) of the CACYBP gene. This alteration results from a C to G substitution at nucleotide position 179, causing the proline (P) at amino acid position 60 to be replaced by an arginine (R). 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	0.24
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	.;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	.;N;D;D
REVEL	Benign	0.13
Sift	Benign	0.082	.;T;D;D
Sift4G	Benign	0.082	T;T;T;T
Polyphen		0.066	.;B;.;.
Vest4		0.25
MutPred		0.68		.;Gain of MoRF binding (P = 0.0268);Gain of MoRF binding (P = 0.0268);.;
MVP		0.45
MPC		0.58
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.72
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-174973913;