chr17-40084775-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_199334.5(THRA):c.536A>G(p.Asn179Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,766 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: 0.0000014 ( 0 hom. )
Consequence
THRA
NM_199334.5 missense
NM_199334.5 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 9.24
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]
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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;
PP2
?
Missense variant where missense usually causes diseases, THRA
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39517692).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THRA | NM_199334.5 | c.536A>G | p.Asn179Ser | missense_variant | 6/9 | ENST00000450525.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THRA | ENST00000450525.7 | c.536A>G | p.Asn179Ser | missense_variant | 6/9 | 1 | NM_199334.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251182Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135818
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461766Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727188
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727188
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ESP6500AA
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0
ESP6500EA
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1
ExAC
?
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1
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | THRA: PM2, PP2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N
REVEL
Uncertain
Sift
Benign
T;.;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;.;.
Vest4
MVP
MPC
0.83
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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