chr17-40083899-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2
The NM_199334.5(THRA):c.287G>A(p.Cys96Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C96F) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
THRA
NM_199334.5 missense
NM_199334.5 missense
Scores
3
9
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.736
Publications
0 publications found
Genes affected
THRA (HGNC:11796): (thyroid hormone receptor alpha) The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
THRA Gene-Disease associations (from GenCC):
- congenital nongoitrous hypothyroidism 6Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the THRA gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 3.4693 (above the threshold of 3.09). Trascript score misZ: 4.6029 (above the threshold of 3.09). GenCC associations: The gene is linked to congenital nongoitrous hypothyroidism 6.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251242 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251242
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T;T;.;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
M;M;M;M;M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N
REVEL
Uncertain
Sift
Benign
T;.;T;T;T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
P;P;P;.;.
Vest4
MutPred
Gain of phosphorylation at C96 (P = 0.0685);Gain of phosphorylation at C96 (P = 0.0685);Gain of phosphorylation at C96 (P = 0.0685);Gain of phosphorylation at C96 (P = 0.0685);Gain of phosphorylation at C96 (P = 0.0685);
MVP
MPC
2.7
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
Publications
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