Variant 5-179705739-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001746.4(CANX):c.58G>T(p.Ala20Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CANX
NM_001746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

Variant links:

Genes affected

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21942315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CANX	NM_001746.4 linkuse as main transcript	c.58G>T	p.Ala20Ser	missense_variant	2/15	ENST00000247461.9	NP_001737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CANX	ENST00000247461.9 linkuse as main transcript	c.58G>T	p.Ala20Ser	missense_variant	2/15	1	NM_001746.4	ENSP00000247461	P3	P27824-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457746

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

GnomAD4 genome

Cov.:

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

Jun 18, 2024

The c.58G>T (p.A20S) alteration is located in exon 2 (coding exon 1) of the CANX gene. This alteration results from a G to T substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 to be replaced by a serine (S). 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

0.099

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

.;T;T;T;T;T;T;T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.86

M_CAP

Benign

0.027

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.81

.;.;L;L;L;.;.;.;.;.

MutationTaster

Benign

0.86

D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.71

N;N;N;N;N;N;N;N;N;D

REVEL

Benign

0.051

Sift

Benign

0.35

T;T;T;T;T;T;D;T;T;D

Sift4G

Benign

0.71

T;T;T;T;T;T;T;T;T;D

Polyphen

0.13

.;.;B;B;B;.;.;.;.;.

Vest4

0.40, 0.40

MutPred

0.28

Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);Loss of catalytic residue at A20 (P = 0.0285);

MVP

0.65

MPC

0.32

ClinPred

0.81

GERP RS

4.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.096

gMVP

0.14

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over