rs10707844
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_000371.4(TTR):c.336+1430_336+1432del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)
Consequence
TTR
NM_000371.4 intron
NM_000371.4 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.206
Genes affected
TTR (HGNC:12405): (transthyretin) This gene encodes one of the three prealbumins, which include alpha-1-antitrypsin, transthyretin and orosomucoid. The encoded protein, transthyretin, is a homo-tetrameric carrier protein, which transports thyroid hormones in the plasma and cerebrospinal fluid. It is also involved in the transport of retinol (vitamin A) in the plasma by associating with retinol-binding protein. The protein may also be involved in other intracellular processes including proteolysis, nerve regeneration, autophagy and glucose homeostasis. Mutations in this gene are associated with amyloid deposition, predominantly affecting peripheral nerves or the heart, while a small percentage of the gene mutations are non-amyloidogenic. The mutations are implicated in the etiology of several diseases, including amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis and carpal tunnel syndrome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BS2
?
High AC in GnomAd4 at 19 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTR | NM_000371.4 | c.336+1430_336+1432del | intron_variant | ENST00000237014.8 | |||
LOC124904277 | XR_007066326.1 | n.129-981_129-979del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTR | ENST00000237014.8 | c.336+1430_336+1432del | intron_variant | 1 | NM_000371.4 | P1 | |||
TTR | ENST00000610404.5 | c.240+1430_240+1432del | intron_variant | 5 | |||||
TTR | ENST00000649620.1 | c.336+1430_336+1432del | intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 19AN: 144866Hom.: 0 Cov.: 0
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GnomAD4 genome ? AF: 0.000131 AC: 19AN: 144866Hom.: 0 Cov.: 0 AF XY: 0.000171 AC XY: 12AN XY: 70242
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ClinVar
Not reported inComputational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at