Genetic Variant BTBD9:p.Arg382His (chr6-38577609-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001099272.2(BTBD9):c.1145G>A(p.Arg382His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,606,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

BTBD9
NM_001099272.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.72

Publications

1 publications found

Variant links:

Genes affected

BTBD9 (HGNC:21228): (BTB domain containing 9) This locus encodes a BTB/POZ domain-containing protein. This domain is known to be involved in protein-protein interactions. Polymorphisms at this locus have been reported to be associated with susceptibility to Restless Legs Syndrome and may also be associated with Tourette Syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2011]

BTBD9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.891

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTBD9	NM_001099272.2	MANE Select	c.1145G>A	p.Arg382His	missense	Exon 6 of 11	NP_001092742.1	Q96Q07-1
BTBD9	NM_052893.2		c.1145G>A	p.Arg382His	missense	Exon 7 of 12	NP_443125.1	Q96Q07-1
BTBD9	NM_001172418.2		c.968G>A	p.Arg323His	missense	Exon 5 of 11	NP_001165889.1	Q96Q07-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTBD9	ENST00000481247.6	TSL:5 MANE Select	c.1145G>A	p.Arg382His	missense	Exon 6 of 11	ENSP00000418751.1	Q96Q07-1
BTBD9	ENST00000419706.6	TSL:1	c.968G>A	p.Arg323His	missense	Exon 5 of 11	ENSP00000415365.2	Q96Q07-2
BTBD9	ENST00000314100.10	TSL:1	c.941G>A	p.Arg314His	missense	Exon 5 of 10	ENSP00000323408.6	Q96Q07-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152096

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

242732

AF XY:

0.00000757

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000563

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1454710

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

723816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33270

American (AMR)

AF:

0.00

AC:

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111068

Other (OTH)

AF:

0.0000166

AC:

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000142

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.000537

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000166

AC:

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

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.49

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.89

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

PhyloP100

7.7

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.84

MVP

0.99

MPC

0.41

ClinPred

0.97

GERP RS

5.7

Varity_R

0.45

gMVP

0.59

Mutation Taster

=39/61

disease causing

(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