Variant 14-24428945-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001039771.3(CBLN3):c.110A>C(p.Glu37Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000901 in 1,553,698 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

CBLN3
NM_001039771.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

Variant links:

Genes affected

CBLN3 (HGNC:20146): (cerebellin 3 precursor) Members of the precerebellin family, such as CBLN3, contain a cerebellin motif (see CBLN1; MIM 600432) and a C-terminal C1q signature domain (see MIM 120550) that mediates trimeric assembly of atypical collagen complexes. However, precerebellins do not contain a collagen motif, suggesting that they are not conventional components of the extracellular matrix (Pang et al., 2000 [PubMed 10964938]).[supplied by OMIM, Aug 2009]

CBLN3 links:

KHNYN (HGNC:20166): (KH and NYN domain containing) The protein encoded by this gene contains a ribonuclease NYN domain and belongs to the N4BP1 family. The protein is a cofactor for the zinc finger antiviral protein (ZAP protein) which targets viral RNA for degradation and restricts SARS-CoV-2 infection. [provided by RefSeq, Sep 2021]

KHNYN links:

Genome browser will be placed here

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=0.36852795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLN3	NM_001039771.3 linkuse as main transcript	c.110A>C	p.Glu37Ala	missense_variant	1/3	ENST00000267406.11	NP_001034860.1	Q6UW01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLN3	ENST00000267406.11 linkuse as main transcript	c.110A>C	p.Glu37Ala	missense_variant	1/3	1	NM_001039771.3	ENSP00000267406.6		Q6UW01
CBLN3	ENST00000555436.1 linkuse as main transcript	c.148-540A>C		intron_variant		3		ENSP00000450935.1		G3V2Y8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000192

AC:

AN:

156576

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000883

Gnomad SAS exome

AF:

0.0000860

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000785

AC:

AN:

1401712

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

691944

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000558

Gnomad4 SAS exome

AF:

0.0000877

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

May 18, 2023

The c.110A>C (p.E37A) alteration is located in exon 1 (coding exon 1) of the CBLN3 gene. This alteration results from a A to C substitution at nucleotide position 110, causing the glutamic acid (E) at amino acid position 37 to be replaced by an alanine (A). 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

0.14

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.37

MetaSVM

Uncertain

0.092

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.63

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.47

MutPred

0.35

Loss of disorder (P = 0.0659);

MVP

0.93

MPC

1.0

ClinPred

0.66

GERP RS

5.2

Varity_R

0.24

gMVP

0.63

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