NM_014962.4:c.1394C>T

Variant summary

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

The NM_014962.4(BTBD3):​c.1394C>T​(p.Thr465Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,614,174 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 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

BTBD3
NM_014962.4 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
BTBD3 (HGNC:15854): (BTB domain containing 3) Enables identical protein binding activity. Predicted to be involved in cerebral cortex development and dendrite morphogenesis. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2613083).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD3NM_014962.4 linkc.1394C>T p.Thr465Ile missense_variant Exon 4 of 4 ENST00000378226.7 NP_055777.1 Q9Y2F9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTBD3ENST00000378226.7 linkc.1394C>T p.Thr465Ile missense_variant Exon 4 of 4 1 NM_014962.4 ENSP00000367471.2 Q9Y2F9-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251376
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.0000344
AC XY:
25
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152282
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1394C>T (p.T465I) alteration is located in exon 4 (coding exon 4) of the BTBD3 gene. This alteration results from a C to T substitution at nucleotide position 1394, causing the threonine (T) at amino acid position 465 to be replaced by an isoleucine (I). 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
Pathogenic
0.22
D
BayesDel_noAF
Pathogenic
0.25
CADD
Benign
22
DANN
Benign
0.95
DEOGEN2
Benign
0.019
.;.;T;.;T;.
Eigen
Benign
0.091
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
.;.;.;.;D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.26
T;T;T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.5
.;.;L;.;L;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.31
N;N;N;.;N;.
REVEL
Uncertain
0.38
Sift
Benign
0.52
T;T;T;.;T;.
Sift4G
Benign
0.21
T;T;T;T;T;T
Polyphen
0.037
.;.;B;.;B;.
Vest4
0.63
MVP
0.89
MPC
0.75
ClinPred
0.18
T
GERP RS
6.0
Varity_R
0.17
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.

Other links and lift over

dbSNP: rs77962945; hg19: chr20-11904139; API