rs121908881
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_ModeratePM1PP3_StrongPP5
The NM_000369.5(TSHR):c.1430C>T(p.Thr477Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T477P) has been classified as Benign.
Frequency
Consequence
NM_000369.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSHR | NM_000369.5 | c.1430C>T | p.Thr477Ile | missense_variant | 10/10 | ENST00000298171.7 | |
LOC101928462 | XR_001751022.2 | n.487+21705G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSHR | ENST00000298171.7 | c.1430C>T | p.Thr477Ile | missense_variant | 10/10 | 1 | NM_000369.5 | P1 | |
ENST00000646052.2 | n.510+21705G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251372Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461758Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727202
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hypothyroidism due to TSH receptor mutations Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2000 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at