5-179679102-G-A

Variant names:

• chr5-179679102-G-A
• rs760010939
• NM_001164444.2:c.210C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001164444.2(CBY3):​c.210C>T​(p.Ser70Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CBY3 NM_001164444.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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]

ENSG00000293215 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.

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.210C>T	p.Ser70Ser	synonymous	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.210C>T	p.Ser70Ser	synonymous	Exon 2 of 2	ENSP00000366173.4	A6NI87
	CANX	ENST00000681712.1		c.-228G>A		5_prime_UTR	Exon 1 of 16	ENSP00000506061.1	P27824-1
	CANX	ENST00000681903.1		c.-186G>A		5_prime_UTR	Exon 1 of 15	ENSP00000506509.1	P27824-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383390 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 682580

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5526

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078672

Other (OTH) AF: 0.00 AC: 0 AN: 57852

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.2
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	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: rs760010939; hg19: chr5-179106103;