NM_152719.3:c.304C>T

Variant names:

• chr13-45713329-C-T
• rs1950283467
• NM_152719.3:c.304C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152719.3(CBY2):​c.304C>T​(p.Pro102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CBY2 NM_152719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.489
• Publications: 0 publications found

Genes affected

CBY2 (HGNC:30720): (chibby family member 2) Enables identical protein binding activity. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048872888).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY2	NM_152719.3	MANE Select	c.304C>T	p.Pro102Ser	missense	Exon 3 of 3	NP_689932.1	Q8NA61-1
	CBY2	NM_001286341.2		c.223C>T	p.Pro75Ser	missense	Exon 2 of 2	NP_001273270.1
	CBY2	NM_001286342.2		c.196C>T	p.Pro66Ser	missense	Exon 3 of 3	NP_001273271.1	Q8NA61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY2	ENST00000310521.6	TSL:1 MANE Select	c.304C>T	p.Pro102Ser	missense	Exon 3 of 3	ENSP00000309189.1	Q8NA61-1
	CBY2	ENST00000378966.3	TSL:1	c.196C>T	p.Pro66Ser	missense	Exon 2 of 2	ENSP00000368249.3	Q8NA61-2
	CBY2	ENST00000610924.1	TSL:5	c.196C>T	p.Pro66Ser	missense	Exon 3 of 3	ENSP00000480148.1	Q8NA61-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.49
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.018
Sift	Benign	0.20	T
Sift4G	Benign	0.28	T
Polyphen		0.041	B
Vest4		0.057
MutPred		0.17		Gain of phosphorylation at P102 (P = 0.0267)
MVP		0.27
MPC		0.35
ClinPred		0.11	T
GERP RS		2.3
Varity_R		0.037
gMVP		0.24
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1950283467; hg19: chr13-46287464;