dbSNP rs1553616532: THRB:p.Thr232_Asn233insGluAlaHisValAlaThr (chr3-24143542-T-TGGTCGCCACATGGGCTTC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001354712.2(THRB):c.679_696dupGAAGCCCATGTGGCGACC(p.Thr232_Asn233insGluAlaHisValAlaThr) variant causes a conservative inframe insertion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

THRB
NM_001354712.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

Genes affected

THRB (HGNC:11799): (thyroid hormone receptor beta) The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]

THRB Gene-Disease associations (from GenCC):

thyroid hormone resistance, generalized, autosomal dominant
Inheritance: SD, AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
thyroid hormone resistance, generalized, autosomal recessive
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

THRB links:

THRB-AS2 (HGNC:):

THRB-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001354712.2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354712.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THRB	NM_001354712.2	MANE Select	c.679_696dupGAAGCCCATGTGGCGACC	p.Thr232_Asn233insGluAlaHisValAlaThr	conservative_inframe_insertion	Exon 8 of 11	NP_001341641.1	P10828-1
THRB	NM_000461.5		c.679_696dupGAAGCCCATGTGGCGACC	p.Thr232_Asn233insGluAlaHisValAlaThr	conservative_inframe_insertion	Exon 7 of 10	NP_000452.2
THRB	NM_001128176.3		c.679_696dupGAAGCCCATGTGGCGACC	p.Thr232_Asn233insGluAlaHisValAlaThr	conservative_inframe_insertion	Exon 8 of 11	NP_001121648.1	P10828-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THRB	ENST00000646209.2	MANE Select	c.679_696dupGAAGCCCATGTGGCGACC	p.Thr232_Asn233insGluAlaHisValAlaThr	conservative_inframe_insertion	Exon 8 of 11	ENSP00000496686.2	P10828-1
THRB	ENST00000356447.9	TSL:1	c.679_696dupGAAGCCCATGTGGCGACC	p.Thr232_Asn233insGluAlaHisValAlaThr	conservative_inframe_insertion	Exon 8 of 11	ENSP00000348827.4	P10828-1
THRB	ENST00000280696.9	TSL:5	c.724_741dupGAAGCCCATGTGGCGACC	p.Thr247_Asn248insGluAlaHisValAlaThr	conservative_inframe_insertion	Exon 4 of 7	ENSP00000280696.5	P10828-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Thyroid hormone resistance, generalized, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over