5-179678771-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164444.2(CBY3):c.541C>G(p.Leu181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,536,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CBY3
NM_001164444.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.730

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14801234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBY3	NM_001164444.2 link	c.541C>G	p.Leu181Val	missense_variant	Exon 2 of 2	ENST00000376974.5	NP_001157916.1	A6NI87
CBY3	XM_047417524.1 link	c.250C>G	p.Leu84Val	missense_variant	Exon 2 of 2		XP_047273480.1
CANX	XM_011534665.4 link	c.-10G>C		5_prime_UTR_variant	Exon 1 of 15		XP_011532967.1	P27824-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CBY3	ENST00000376974.5 link	c.541C>G	p.Leu181Val	missense_variant	Exon 2 of 2	2	NM_001164444.2	ENSP00000366173.4	A6NI87
CANX	ENST00000681674 link	c.-10G>C		5_prime_UTR_variant	Exon 1 of 15			ENSP00000505013.1	P27824-1
CANX	ENST00000681712 link	c.-559G>C		5_prime_UTR_variant	Exon 1 of 16			ENSP00000506061.1	P27824-1
CANX	ENST00000681903 link	c.-517G>C		5_prime_UTR_variant	Exon 1 of 15			ENSP00000506509.1	P27824-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000210

AC:

AN:

142718

Hom.:

AF XY:

0.0000393

AC XY:

AN XY:

76358

show subpopulations

Gnomad AFR exome

AF:

0.000263

Gnomad AMR exome

AF:

0.0000407

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1384722

Hom.:

Cov.:

AF XY:

0.0000176

AC XY:

AN XY:

683306

show subpopulations

Gnomad4 AFR exome

AF:

0.000507

Gnomad4 AMR exome

AF:

0.0000280

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:

0.00

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.000151

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000261

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.541C>G (p.L181V) alteration is located in exon 2 (coding exon 2) of the CBY3 gene. This alteration results from a C to G substitution at nucleotide position 541, causing the leucine (L) at amino acid position 181 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.83

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.15

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Uncertain

0.019

Sift4G

Pathogenic

0.0

Vest4

0.36

MutPred

0.19

Gain of methylation at K180 (P = 0.0383);

MVP

0.088

ClinPred

0.68

GERP RS

4.3

Varity_R

0.31

gMVP

0.31

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