14-80955786-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000369.5(TSHR):āc.106G>Cā(p.Asp36His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00697 in 1,614,204 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.
Frequency
Consequence
NM_000369.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSHR | NM_000369.5 | c.106G>C | p.Asp36His | missense_variant | Exon 1 of 10 | ENST00000298171.7 | NP_000360.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSHR | ENST00000298171.7 | c.106G>C | p.Asp36His | missense_variant | Exon 1 of 10 | 1 | NM_000369.5 | ENSP00000298171.2 |
Frequencies
GnomAD3 genomes AF: 0.00485 AC: 738AN: 152212Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.00517 AC: 1294AN: 250062Hom.: 10 AF XY: 0.00532 AC XY: 719AN XY: 135272
GnomAD4 exome AF: 0.00719 AC: 10511AN: 1461874Hom.: 43 Cov.: 31 AF XY: 0.00700 AC XY: 5091AN XY: 727234
GnomAD4 genome AF: 0.00484 AC: 738AN: 152330Hom.: 4 Cov.: 33 AF XY: 0.00475 AC XY: 354AN XY: 74482
ClinVar
Submissions by phenotype
not provided Benign:3
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TSHR: BP4, BS2 -
not specified Benign:2Other:1
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Hypothyroidism due to TSH receptor mutations 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Graves disease, susceptibility to, 1 Benign:1
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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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at