13-45713421-C-G

Variant names:

• chr13-45713421-C-G
• rs143335236
• NM_152719.3:c.396C>G

Variant summary

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

The NM_152719.3(CBY2):​c.396C>G​(p.Asp132Glu) 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 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• 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: -0.271

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

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=0.29187116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBY2	NM_152719.3	c.396C>G	p.Asp132Glu	missense_variant	Exon 3 of 3	ENST00000310521.6	NP_689932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBY2	ENST00000310521.6	c.396C>G	p.Asp132Glu	missense_variant	Exon 3 of 3	1	NM_152719.3	ENSP00000309189.1
CBY2	ENST00000378966.3	c.288C>G	p.Asp96Glu	missense_variant	Exon 2 of 2	1		ENSP00000368249.3
CBY2	ENST00000610924.1	c.288C>G	p.Asp96Glu	missense_variant	Exon 3 of 3	5		ENSP00000480148.1
CBY2	ENST00000533564.1	c.315C>G	p.Asp105Glu	missense_variant	Exon 2 of 2	2		ENSP00000435230.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251370 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;.;.;.
Eigen	Benign	0.030
Eigen_PC	Benign	-0.0056
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.69	T;T;T;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N;N;.;N
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D;D;.;D
Sift4G	Benign	0.17	T;D;T;T
Polyphen		1.0	D;.;D;D
Vest4		0.60
MutPred		0.49		Gain of sheet (P = 0.1208);.;.;.;
MVP		0.49
MPC		1.1
ClinPred		0.90	D
GERP RS		1.2
Varity_R		0.12
gMVP		0.25

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: rs143335236; hg19: chr13-46287556;