Genetic Variant NM_001387567.1:c.179C>G (chr14-105248890-C-G) – 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.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

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]

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=0.111497074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD6	NM_001387567.1 link	c.179C>G	p.Ala60Gly	missense_variant	Exon 1 of 4	ENST00000392554.8	NP_001374496.1
BRF1	NM_001519.4 link	c.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
BTBD6	ENST00000392554.8 link	c.179C>G	p.Ala60Gly	missense_variant	Exon 1 of 4	1	NM_001387567.1	ENSP00000376337.4		Q96KE9-3A0A8C8KHP4
BRF1	ENST00000547530.7 link	c.544+3617G>C		intron_variant	Intron 5 of 17	1	NM_001519.4	ENSP00000448387.2		Q92994-1

Frequencies

GnomAD3 genomes

AF:

0.0000685

AC:

AN:

145962

Hom.:

Cov.:

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:

AN:

842008

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

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:

AN:

145962

Hom.:

Cov.:

AF XY:

0.0000563

AC XY:

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

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.032

T;.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.31

T;T;.

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.;N

PrimateAI

Uncertain

0.73

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

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.

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