rs189506473
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000369.5(TSHR):c.733G>A(p.Gly245Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000369.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSHR | NM_000369.5 | c.733G>A | p.Gly245Ser | missense_variant | Exon 9 of 10 | ENST00000298171.7 | NP_000360.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSHR | ENST00000298171.7 | c.733G>A | p.Gly245Ser | missense_variant | Exon 9 of 10 | 1 | NM_000369.5 | ENSP00000298171.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251472Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135912
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727244
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74450
ClinVar
Submissions by phenotype
Hypothyroidism due to TSH receptor mutations Uncertain:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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not provided Uncertain:1
Identified in the heterozygous state in several individuals with congenital hypothyroidism; however, evidence in support of pathogenicity for this variant was not provided in the report and some individuals also had variants in other genes associated with congenital hypothyroidism (Yuan et al., 2008; Long et al., 2018; Makretskaya et al., 2018; Lee et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17953807, 21714469, 18379122, 30022773, 30240412, 21707688, 20083154, 32459320) -
Familial hyperthyroidism due to mutations in TSH receptor Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at