chr1-23397845-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003196.3(TCEA3):c.554A>T(p.Asp185Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,676 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: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TCEA3
NM_003196.3 missense
NM_003196.3 missense
Scores
7
9
2
Clinical Significance
Conservation
PhyloP100: 7.59
Genes affected
TCEA3 (HGNC:11615): (transcription elongation factor A3) Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in regulation of transcription, DNA-templated and transcription, DNA-templated. Predicted to be located in 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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.911
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461676Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727128
GnomAD4 exome
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1
AN:
1461676
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32
AF XY:
AC XY:
1
AN XY:
727128
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
Bravo
AF:
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 26, 2024 | The c.554A>T (p.D185V) alteration is located in exon 6 (coding exon 6) of the TCEA3 gene. This alteration results from a A to T substitution at nucleotide position 554, causing the aspartic acid (D) at amino acid position 185 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
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Loss of disorder (P = 0.0427);.;
MVP
MPC
ClinPred
D
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