NM_001387567.1:c.179C>G

Variant summary

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

The NM_001387567.1(BTBD6):​c.179C>G​(p.Ala60Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000486 in 987,970 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: 𝑓 0.000069 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

BTBD6
NM_001387567.1 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27
Variant links:
Genes affected
BTBD6 (HGNC:19897): (BTB domain containing 6) Predicted to be involved in neurogenesis. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
BRF1 (HGNC:11551): (BRF1 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Several alternatively spliced variants encoding different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. [provided by RefSeq, Jun 2011]

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=0.111497074).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD6NM_001387567.1 linkc.179C>G p.Ala60Gly missense_variant Exon 1 of 4 ENST00000392554.8 NP_001374496.1
BRF1NM_001519.4 linkc.544+3617G>C intron_variant Intron 5 of 17 ENST00000547530.7 NP_001510.2 Q92994-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTBD6ENST00000392554.8 linkc.179C>G p.Ala60Gly missense_variant Exon 1 of 4 1 NM_001387567.1 ENSP00000376337.4 Q96KE9-3A0A8C8KHP4
BRF1ENST00000547530.7 linkc.544+3617G>C intron_variant Intron 5 of 17 1 NM_001519.4 ENSP00000448387.2 Q92994-1

Frequencies

GnomAD3 genomes
AF:
0.0000685
AC:
10
AN:
145962
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000493
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00236
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000451
AC:
38
AN:
842008
Hom.:
0
Cov.:
30
AF XY:
0.0000385
AC XY:
15
AN XY:
389572
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00353
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000130
Gnomad4 OTH exome
AF:
0.000324
GnomAD4 genome
AF:
0.0000685
AC:
10
AN:
145962
Hom.:
0
Cov.:
32
AF XY:
0.0000563
AC XY:
4
AN XY:
70990
show subpopulations
Gnomad4 AFR
AF:
0.0000493
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00236
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000128

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.20C>G (p.A7G) alteration is located in exon 2 (coding exon 1) of the BTBD6 gene. This alteration results from a C to G substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 to be replaced by a glycine (G). 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
0.089
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.032
T;.;T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.31
T;T;.
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N;.;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.18
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.047
D;D;D
Sift4G
Benign
0.38
T;T;T
Polyphen
0.0030
B;.;B
Vest4
0.18
MutPred
0.12
Gain of catalytic residue at A7 (P = 0.0207);Gain of catalytic residue at A7 (P = 0.0207);Gain of catalytic residue at A7 (P = 0.0207);
MVP
0.56
MPC
0.39
ClinPred
0.13
T
GERP RS
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.066
gMVP
0.49

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: rs1165699455; hg19: chr14-105715227; API