chr6-38577699-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001099272.2(BTBD9):c.1055A>T(p.Glu352Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000541 in 1,609,014 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
BTBD9
NM_001099272.2 missense
NM_001099272.2 missense
Scores
12
4
1
Clinical Significance
Conservation
PhyloP100: 7.83
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BTBD9 | NM_001099272.2 | c.1055A>T | p.Glu352Val | missense_variant | 6/11 | ENST00000481247.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTBD9 | ENST00000481247.6 | c.1055A>T | p.Glu352Val | missense_variant | 6/11 | 5 | NM_001099272.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152086Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000982 AC: 24AN: 244446Hom.: 1 AF XY: 0.000113 AC XY: 15AN XY: 132960
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GnomAD4 exome AF: 0.0000522 AC: 76AN: 1456928Hom.: 0 Cov.: 30 AF XY: 0.0000524 AC XY: 38AN XY: 724974
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152086Hom.: 1 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74274
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 23, 2023 | The c.1055A>T (p.E352V) alteration is located in exon 7 (coding exon 5) of the BTBD9 gene. This alteration results from a A to T substitution at nucleotide position 1055, causing the glutamic acid (E) at amino acid position 352 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;D;.;D
REVEL
Pathogenic
Sift
Uncertain
D;D;.;D;.;D
Sift4G
Pathogenic
D;D;.;D;D;D
Polyphen
1.0
.;D;D;.;.;.
Vest4
MutPred
0.60
.;Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);.;.;Loss of sheet (P = 0.007);
MVP
MPC
0.39
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at