rs121912646
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003235.5(TG):c.4588C>G(p.Arg1530Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Consequence
TG
NM_003235.5 missense
NM_003235.5 missense
Scores
6
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.83
Genes affected
TG (HGNC:11764): (thyroglobulin) Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31259137).
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TG | ENST00000220616.9 | c.4588C>G | p.Arg1530Gly | missense_variant | Exon 22 of 48 | 1 | NM_003235.5 | ENSP00000220616.4 | ||
TG | ENST00000523756.5 | n.*801C>G | non_coding_transcript_exon_variant | Exon 9 of 35 | 1 | ENSP00000428628.1 | ||||
TG | ENST00000523756.5 | n.*801C>G | 3_prime_UTR_variant | Exon 9 of 35 | 1 | ENSP00000428628.1 | ||||
TG | ENST00000519178.5 | c.145C>G | p.Arg49Gly | missense_variant | Exon 2 of 27 | 2 | ENSP00000430523.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251390Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135862
GnomAD3 exomes
AF:
AC:
1
AN:
251390
Hom.:
AF XY:
AC XY:
0
AN XY:
135862
Gnomad AFR exome
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of MoRF binding (P = 0.0372);
MVP
MPC
ClinPred
T
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