Variant 8-87206007-C-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_173538.3(CNBD1):c.446C>T(p.Thr149Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,526,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CNBD1
NM_173538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.200

Variant links:

Genes affected

CNBD1 (HGNC:26663): (cyclic nucleotide binding domain containing 1)

CNBD1 links:

CNBD1 (HGNC:):

CNBD1 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=0.13111082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNBD1	NM_173538.3 linkuse as main transcript	c.446C>T	p.Thr149Met	missense_variant	5/11	ENST00000518476.6	NP_775809.1	Q8NA66
CNBD1	XM_017013149.2 linkuse as main transcript	c.446C>T	p.Thr149Met	missense_variant	5/11		XP_016868638.1
CNBD1	XM_024447082.2 linkuse as main transcript	c.446C>T	p.Thr149Met	missense_variant	5/7		XP_024302850.1
CNBD1	XM_047421411.1 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	4/7		XP_047277367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNBD1	ENST00000518476.6 linkuse as main transcript	c.446C>T	p.Thr149Met	missense_variant	5/11	1	NM_173538.3	ENSP00000430073.1	Q8NA66
CNBD1	ENST00000523299.6 linkuse as main transcript	c.446C>T	p.Thr149Met	missense_variant	5/13	3		ENSP00000430986.2	H0YC59
CNBD1	ENST00000522427.1 linkuse as main transcript	n.189C>T		non_coding_transcript_exon_variant	2/4	4
CNBD1	ENST00000522105.1 linkuse as main transcript	n.-41C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000194

AC:

AN:

149162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

172808

Hom.:

AF XY:

0.0000213

AC XY:

AN XY:

94036

show subpopulations

Gnomad AFR exome

AF:

0.000485

Gnomad AMR exome

AF:

0.00

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:

0.0000247

Gnomad OTH exome

AF:

0.000247

GnomAD4 exome

AF:

0.0000334

AC:

AN:

1377662

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

682622

show subpopulations

Gnomad4 AFR exome

AF:

0.000650

Gnomad4 AMR exome

AF:

0.0000325

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000555

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000177

Gnomad4 OTH exome

AF:

0.0000705

GnomAD4 genome

AF:

0.000194

AC:

AN:

149162

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

72564

show subpopulations

Gnomad4 AFR

AF:

0.000672

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000825

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000249

AC:

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

Dec 27, 2023

The c.446C>T (p.T149M) alteration is located in exon 5 (coding exon 5) of the CNBD1 gene. This alteration results from a C to T substitution at nucleotide position 446, causing the threonine (T) at amino acid position 149 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.062

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.13

T;T

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

0.81

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.2

D;.

REVEL

Uncertain

0.38

Sift

Benign

0.068

T;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;.

Vest4

0.30

MVP

0.34

MPC

0.0081

ClinPred

0.12

GERP RS

4.1

Varity_R

0.033

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