14-55428933-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_199047.3(TBPL2):āc.734T>Cā(p.Val245Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,884 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000011 ( 1 hom. )
Consequence
TBPL2
NM_199047.3 missense
NM_199047.3 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 8.97
Genes affected
TBPL2 (HGNC:19841): (TATA-box binding protein like 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Predicted to be involved in DNA-templated transcription, initiation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|
TBPL2 | NM_199047.3 | c.734T>C | p.Val245Ala | missense_variant | 5/7 | ENST00000247219.6 | |
FBXO34 | XR_007064022.1 | n.2982+4849A>G | intron_variant, non_coding_transcript_variant | ||||
FBXO34 | XR_007064023.1 | n.2941-13894A>G | intron_variant, non_coding_transcript_variant | ||||
FBXO34 | XR_007064024.1 | n.2982+4849A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBPL2 | ENST00000247219.6 | c.734T>C | p.Val245Ala | missense_variant | 5/7 | 1 | NM_199047.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251464Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461884Hom.: 1 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727240
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GnomAD4 genome Cov.: 32
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32
ExAC
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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 | Sep 21, 2023 | The c.830T>C (p.V277A) alteration is located in exon 5 (coding exon 5) of the TBPL2 gene. This alteration results from a T to C substitution at nucleotide position 830, causing the valine (V) at amino acid position 277 to be replaced by an alanine (A). 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of stability (P = 0.0469);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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