chr6-133980193-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004865.4(TBPL1):c.68G>A(p.Arg23Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TBPL1
NM_004865.4 missense
NM_004865.4 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 9.46
Genes affected
TBPL1 (HGNC:11589): (TATA-box binding protein like 1) This gene encodes a member of the TATA box-binding protein family. TATA box-binding proteins play a critical role in transcription by RNA polymerase II as components of the transcription factor IID (TFIID) complex. The encoded protein does not bind to the TATA box and initiates transcription from TATA-less promoters. This gene plays a critical role in spermatogenesis, and single nucleotide polymorphisms in this gene may be associated with male infertility. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 3. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3618962).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247676Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133946
GnomAD3 exomes
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247676
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133946
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457602Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724986
GnomAD4 exome
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30
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724986
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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1
Asia WGS
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1
AN:
3478
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 | Jul 02, 2024 | The c.68G>A (p.R23K) alteration is located in exon 2 (coding exon 1) of the TBPL1 gene. This alteration results from a G to A substitution at nucleotide position 68, causing the arginine (R) at amino acid position 23 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.;L;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;T;T;T;T
Sift4G
Benign
T;T;D;T;T;T
Polyphen
0.20
.;B;.;.;B;.
Vest4
0.60, 0.59
MutPred
Gain of methylation at R23 (P = 0.0126);Gain of methylation at R23 (P = 0.0126);Gain of methylation at R23 (P = 0.0126);Gain of methylation at R23 (P = 0.0126);Gain of methylation at R23 (P = 0.0126);Gain of methylation at R23 (P = 0.0126);
MVP
MPC
1.3
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at