GeneBe

rs760001658

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001099272.2(BTBD9):​c.1078T>G​(p.Trp360Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. W360R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

BTBD9
NM_001099272.2 missense

Scores

15
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.10

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BTBD9
NM_001099272.2
MANE Select
c.1078T>Gp.Trp360Gly
missense
Exon 6 of 11NP_001092742.1Q96Q07-1
BTBD9
NM_052893.2
c.1078T>Gp.Trp360Gly
missense
Exon 7 of 12NP_443125.1Q96Q07-1
BTBD9
NM_001172418.2
c.901T>Gp.Trp301Gly
missense
Exon 5 of 11NP_001165889.1Q96Q07-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BTBD9
ENST00000481247.6
TSL:5 MANE Select
c.1078T>Gp.Trp360Gly
missense
Exon 6 of 11ENSP00000418751.1Q96Q07-1
BTBD9
ENST00000419706.6
TSL:1
c.901T>Gp.Trp301Gly
missense
Exon 5 of 11ENSP00000415365.2Q96Q07-2
BTBD9
ENST00000314100.10
TSL:1
c.874T>Gp.Trp292Gly
missense
Exon 5 of 10ENSP00000323408.6Q96Q07-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000406
AC:
1
AN:
246108
AF XY:
0.00000747
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
28
DANN
Uncertain
0.98
DEOGEN2
Pathogenic
0.90
D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.81
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
3.1
M
PhyloP100
9.1
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-12
D
REVEL
Pathogenic
0.93
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.92
Loss of catalytic residue at L358 (P = 0.0057)
MVP
0.98
MPC
0.59
ClinPred
1.0
D
GERP RS
5.7
Varity_R
0.97
gMVP
0.87
Mutation Taster
=14/86
disease causing

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

Other links and lift over

dbSNP: rs760001658; hg19: chr6-38545452; API