Variant 5-179679095-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001164444.2(CBY3):c.217T>G(p.Trp73Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,535,830 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

CBY3
NM_001164444.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

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

CBY3 links:

(HGNC:):

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:

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ACMG classification

Classification made for transcript

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=0.29488838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CBY3	NM_001164444.2 linkuse as main transcript	c.217T>G	p.Trp73Gly	missense_variant	2/2	ENST00000376974.5	NP_001157916.1
CBY3	XM_047417524.1 linkuse as main transcript	c.-75T>G		5_prime_UTR_variant	2/2		XP_047273480.1
CANX	XM_011534665.4 linkuse as main transcript	c.-4+318A>C		intron_variant			XP_011532967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBY3	ENST00000376974.5 linkuse as main transcript	c.217T>G	p.Trp73Gly	missense_variant	2/2	2	NM_001164444.2	ENSP00000366173	P1
	ENST00000442010.2 linkuse as main transcript	n.64A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000402

AC:

AN:

134476

Hom.:

AF XY:

0.000385

AC XY:

AN XY:

72812

show subpopulations

Gnomad AFR exome

AF:

0.000147

Gnomad AMR exome

AF:

0.000490

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000927

Gnomad NFE exome

AF:

0.000611

Gnomad OTH exome

AF:

0.000976

GnomAD4 exome

AF:

0.000715

AC:

989

AN:

1383438

Hom.:

Cov.:

AF XY:

0.000690

AC XY:

471

AN XY:

682600

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000420

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000824

Gnomad4 NFE exome

AF:

0.000847

Gnomad4 OTH exome

AF:

0.000432

GnomAD4 genome

AF:

0.000394

AC:

AN:

152392

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000336

ExAC

AF:

0.000137

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.217T>G (p.W73G) alteration is located in exon 2 (coding exon 2) of the CBY3 gene. This alteration results from a T to G substitution at nucleotide position 217, causing the tryptophan (W) at amino acid position 73 to be replaced by a glycine (G). 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

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.014

Eigen

Benign

-0.024

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.56

M_CAP

Benign

0.075

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.96

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.19

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Vest4

0.68

MVP

0.19

ClinPred

0.56

GERP RS

3.4

Varity_R

0.40

gMVP

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over