Genetic Variant CBY3:p.Thr75Ala (chr5-179679089-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164444.2(CBY3):c.223A>G(p.Thr75Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,383,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000029 ( 0 hom. )

Consequence

CBY3
NM_001164444.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Publications

0 publications found

Variant links:

Genes affected

CBY3 (HGNC:33278): (chibby family member 3)

CBY3 links:

CANX (HGNC:1473): (calnexin) This gene encodes a member of the calnexin family of molecular chaperones. The encoded protein is a calcium-binding, endoplasmic reticulum (ER)-associated protein that interacts transiently with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. It may also play a central role in the quality control of protein folding by retaining incorrectly folded protein subunits within the ER for degradation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2018]

CANX links:

ENSG00000293215 (HGNC:):

ENSG00000293215 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1101501).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164444.2. 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
	CBY3	NM_001164444.2	MANE Select	c.223A>G	p.Thr75Ala	missense	Exon 2 of 2	NP_001157916.1	A6NI87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBY3	ENST00000376974.5	TSL:2 MANE Select	c.223A>G	p.Thr75Ala	missense	Exon 2 of 2	ENSP00000366173.4	A6NI87
CANX	ENST00000681712.1		c.-241T>C		5_prime_UTR	Exon 1 of 16	ENSP00000506061.1	P27824-1
CANX	ENST00000681903.1		c.-199T>C		5_prime_UTR	Exon 1 of 15	ENSP00000506509.1	P27824-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000743

AC:

AN:

134512

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000952

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1383398

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

682586

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31584

American (AMR)

AF:

0.00

AC:

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.000112

AC:

AN:

35724

South Asian (SAS)

AF:

0.00

AC:

AN:

79198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078620

Other (OTH)

AF:

0.00

AC:

AN:

57864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.0065

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.4

PrimateAI

Benign

0.45

PROVEAN

Benign

0.13

REVEL

Benign

0.047

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.043

Vest4

0.13

MutPred

0.21

Loss of MoRF binding (P = 0.1342)

MVP

0.030

ClinPred

0.14

GERP RS

3.8

PromoterAI

-0.0041

Neutral

(source)

Varity_R

0.069

gMVP

0.25

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over