dbSNP rs1027752644: BTBD6:p.Gln110Lys (chr14-105249039-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001387567.1(BTBD6):c.328C>A(p.Gln110Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000009 in 1,110,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q110E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

BTBD6
NM_001387567.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.322

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]

BTBD6 links:

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]

BRF1 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=0.07163045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD6	NM_001387567.1 link	c.328C>A	p.Gln110Lys	missense_variant	Exon 1 of 4	ENST00000392554.8	NP_001374496.1
BRF1	NM_001519.4 link	c.544+3468G>T		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
BTBD6	ENST00000392554.8 link	c.328C>A	p.Gln110Lys	missense_variant	Exon 1 of 4	1	NM_001387567.1	ENSP00000376337.4		Q96KE9-3A0A8C8KHP4
BRF1	ENST00000547530.7 link	c.544+3468G>T		intron_variant	Intron 5 of 17	1	NM_001519.4	ENSP00000448387.2		Q92994-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.00e-7

AC:

AN:

1110724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

535324

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.059

DANN

Benign

0.66

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.26

T;T;.

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;.;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.96

T;T;T

Polyphen

0.0020

B;.;B

Vest4

0.093

MutPred

0.31

Gain of ubiquitination at Q57 (P = 0.0045);Gain of ubiquitination at Q57 (P = 0.0045);Gain of ubiquitination at Q57 (P = 0.0045);

MVP

0.38

MPC

0.51

ClinPred

0.12

GERP RS

-5.4

Varity_R

0.049

gMVP

0.32

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

Computational scores

Splicing

Publications

Other links and lift over