5-179678749-T-A

Variant names:

• chr5-179678749-T-A
• rs2127760214
• NM_001164444.2:c.563A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001164444.2(CBY3):​c.563A>T​(p.Asp188Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBY3 NM_001164444.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

Genes affected

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

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]

ENSG00000250999 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.563A>T	p.Asp188Val	missense	Exon 2 of 2	NP_001157916.1	A6NI87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY3	ENST00000376974.5	TSL:2 MANE Select	c.563A>T	p.Asp188Val	missense	Exon 2 of 2	ENSP00000366173.4	A6NI87
	CANX	ENST00000681674.1		c.-32T>A		5_prime_UTR	Exon 1 of 15	ENSP00000505013.1	P27824-1
	CANX	ENST00000681712.1		c.-581T>A		5_prime_UTR	Exon 1 of 16	ENSP00000506061.1	P27824-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.80
MutPred		0.42		Gain of catalytic residue at D188 (P = 0.0047)
MVP		0.28
ClinPred		1.0	D
GERP RS		5.0
PromoterAI		0.060	Neutral
Varity_R		0.87
gMVP		0.67
Mutation Taster		=79/21	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: rs2127760214; hg19: chr5-179105750;