15-83041884-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_025238.4(BTBD1):c.706C>G(p.Arg236Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
BTBD1
NM_025238.4 missense
NM_025238.4 missense
Scores
6
12
1
Clinical Significance
Conservation
PhyloP100: 5.07
Genes affected
BTBD1 (HGNC:1120): (BTB domain containing 1) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.872
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BTBD1 | NM_025238.4 | c.706C>G | p.Arg236Gly | missense_variant | 4/8 | ENST00000261721.9 | |
LOC124903542 | XR_007064742.1 | n.1320-19603G>C | intron_variant, non_coding_transcript_variant | ||||
BTBD1 | NM_001011885.2 | c.706C>G | p.Arg236Gly | missense_variant | 4/7 | ||
BTBD1 | XR_007064459.1 | n.807C>G | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTBD1 | ENST00000261721.9 | c.706C>G | p.Arg236Gly | missense_variant | 4/8 | 1 | NM_025238.4 | P1 | |
ENST00000566841.1 | n.735-61540G>C | intron_variant, non_coding_transcript_variant | 5 | ||||||
ENST00000568441.1 | n.37+19277G>C | intron_variant, non_coding_transcript_variant | 5 | ||||||
ENST00000570202.1 | n.63-19603G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251464Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727232
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN 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 | Dec 28, 2022 | The c.706C>G (p.R236G) alteration is located in exon 4 (coding exon 4) of the BTBD1 gene. This alteration results from a C to G substitution at nucleotide position 706, causing the arginine (R) at amino acid position 236 to be replaced by a glycine (G). 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
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0673);Loss of MoRF binding (P = 0.0673);
MVP
MPC
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