chr17-37437804-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001166105.3(TADA2A):​c.259G>A​(p.Val87Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TADA2A
NM_001166105.3 missense

Scores

8
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.88
Variant links:
Genes affected
TADA2A (HGNC:11531): (transcriptional adaptor 2A) Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated gene transcription by interacting functionally with the general transcription machinery bound at the basal promoter. Adaptor proteins are usually required for this activation, possibly to acetylate and destabilize nucleosomes, thereby relieving chromatin constraints at the promoter. The protein encoded by this gene is a transcriptional activator adaptor and has been found to be part of the PCAF histone acetylase complex. Several alternatively spliced transcript variants encoding different isoforms of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2009]

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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, 0.859

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TADA2ANM_001166105.3 linkuse as main transcriptc.259G>A p.Val87Met missense_variant 5/16 ENST00000615182.5 NP_001159577.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TADA2AENST00000615182.5 linkuse as main transcriptc.259G>A p.Val87Met missense_variant 5/165 NM_001166105.3 ENSP00000481091 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsOct 02, 2023The c.259G>A (p.V87M) alteration is located in exon 5 (coding exon 4) of the TADA2A gene. This alteration results from a G to A substitution at nucleotide position 259, causing the valine (V) at amino acid position 87 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
T;T;T;.;.
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D;.;.
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.86
D;D;D;D;D
MetaSVM
Uncertain
-0.21
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.79
T
Sift4G
Uncertain
0.033
D;D;D;D;D
Vest4
0.80
MutPred
0.68
Gain of disorder (P = 0.2478);Gain of disorder (P = 0.2478);Gain of disorder (P = 0.2478);.;.;
MVP
0.48
ClinPred
0.93
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-35797905; API