chr13-45713356-G-T

Variant names:

• chr13-45713356-G-T
• rs534915627
• NM_152719.3:c.331G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152719.3(CBY2):​c.331G>T​(p.Asp111Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D111N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CBY2 NM_152719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3766312).

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.331G>T	p.Asp111Tyr	missense	Exon 3 of 3	NP_689932.1	Q8NA61-1
	CBY2	NM_001286341.2		c.250G>T	p.Asp84Tyr	missense	Exon 2 of 2	NP_001273270.1
	CBY2	NM_001286342.2		c.223G>T	p.Asp75Tyr	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.331G>T	p.Asp111Tyr	missense	Exon 3 of 3	ENSP00000309189.1	Q8NA61-1
	CBY2	ENST00000378966.3	TSL:1	c.223G>T	p.Asp75Tyr	missense	Exon 2 of 2	ENSP00000368249.3	Q8NA61-2
	CBY2	ENST00000610924.1	TSL:5	c.223G>T	p.Asp75Tyr	missense	Exon 3 of 3	ENSP00000480148.1	Q8NA61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

African (AFR) AF: 0.0000299 AC: 1 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: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.9	M
PhyloP100		4.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.25		Gain of phosphorylation at D111 (P = 0.0103)
MVP		0.76
MPC		1.2
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.48
gMVP		0.48
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs534915627; hg19: chr13-46287491;