rs121908868
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PS1_ModeratePP5
The NM_000369.5(TSHR):c.1228G>A(p.Asp410Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Synonymous variant affecting the same amino acid position (i.e. D410D) has been classified as Likely benign.
Frequency
Consequence
NM_000369.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSHR | NM_000369.5 | c.1228G>A | p.Asp410Asn | missense_variant | 10/10 | ENST00000298171.7 | |
LOC101928462 | XR_001751022.2 | n.487+21907C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSHR | ENST00000298171.7 | c.1228G>A | p.Asp410Asn | missense_variant | 10/10 | 1 | NM_000369.5 | P1 | |
ENST00000646052.2 | n.510+21907C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461890Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727248
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hypothyroidism due to TSH receptor mutations Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 1996 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at