14-105248982-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387567.1(BTBD6):c.271C>T(p.Pro91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 986,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

BTBD6
NM_001387567.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

cerebellar-facial-dental syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
colorectal adenoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15427735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387567.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTBD6	NM_001387567.1	MANE Select	c.271C>T	p.Pro91Ser	missense	Exon 1 of 4	NP_001374496.1	A0A8C8KHP4
BRF1	NM_001519.4	MANE Select	c.544+3525G>A		intron	N/A	NP_001510.2
BTBD6	NM_033271.3		c.112C>T	p.Pro38Ser	missense	Exon 2 of 5	NP_150374.2	Q96KE9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTBD6	ENST00000392554.8	TSL:1 MANE Select	c.271C>T	p.Pro91Ser	missense	Exon 1 of 4	ENSP00000376337.4	Q96KE9-3
BRF1	ENST00000547530.7	TSL:1 MANE Select	c.544+3525G>A		intron	N/A	ENSP00000448387.2	Q92994-1
BRF1	ENST00000379937.6	TSL:1	c.463+3525G>A		intron	N/A	ENSP00000369269.2	Q92994-5

Frequencies

GnomAD3 genomes

AF:

0.0000274

AC:

AN:

145958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000609

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000714

AC:

AN:

840406

Hom.:

Cov.:

AF XY:

0.00000770

AC XY:

AN XY:

389362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15816

American (AMR)

AF:

0.00

AC:

AN:

1344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5352

East Asian (EAS)

AF:

0.00

AC:

AN:

4006

South Asian (SAS)

AF:

0.00

AC:

AN:

17318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1646

European-Non Finnish (NFE)

AF:

0.00000783

AC:

AN:

765832

Other (OTH)

AF:

0.00

AC:

AN:

27790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000274

AC:

AN:

145958

Hom.:

Cov.:

AF XY:

0.0000423

AC XY:

AN XY:

70976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40700

American (AMR)

AF:

0.00

AC:

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000609

AC:

AN:

65734

Other (OTH)

AF:

0.00

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.021

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

3.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.65

REVEL

Benign

0.095

Sift

Benign

0.87

Sift4G

Benign

0.49

Polyphen

0.0020

Vest4

0.094

MutPred

0.24

Gain of phosphorylation at P38 (P = 0.0031)

MVP

0.45

MPC

0.40

ClinPred

0.11

GERP RS

2.6

PromoterAI

0.19

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.031

gMVP

0.34

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over