rs202208051
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_147196.3(TMIE):c.219G>A(p.Thr73Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_147196.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMIE | NM_147196.3 | c.219G>A | p.Thr73Thr | synonymous_variant | Exon 3 of 4 | ENST00000643606.3 | NP_671729.2 | |
TMIE | NM_001370524.1 | c.60G>A | p.Thr20Thr | synonymous_variant | Exon 3 of 4 | NP_001357453.1 | ||
TMIE | NM_001370525.1 | c.60G>A | p.Thr20Thr | synonymous_variant | Exon 4 of 5 | NP_001357454.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMIE | ENST00000643606.3 | c.219G>A | p.Thr73Thr | synonymous_variant | Exon 3 of 4 | NM_147196.3 | ENSP00000494576.2 | |||
TMIE | ENST00000644830.1 | c.60G>A | p.Thr20Thr | synonymous_variant | Exon 3 of 4 | ENSP00000495111.1 | ||||
TMIE | ENST00000651652.1 | c.117G>A | p.Thr39Thr | synonymous_variant | Exon 2 of 2 | ENSP00000498953.1 |
Frequencies
GnomAD3 genomes AF: 0.000526 AC: 80AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000152 AC: 38AN: 249232Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135266
GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461730Hom.: 0 Cov.: 34 AF XY: 0.0000756 AC XY: 55AN XY: 727174
GnomAD4 genome AF: 0.000519 AC: 79AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32AN XY: 74504
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
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TMIE: BP4, BP7 -
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not specified Benign:2
BP6, BP7; This alteration was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory), and is a synonymous alteration with no predicted impact on splicing and/or occurring at a non-evolutionarily conserved nucleotide position. -
p.Thr73Thr in exon 03 of TMIE: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.2% (15/9778) of Afr ican chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs202208051). -
Autosomal recessive nonsyndromic hearing loss 6 Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
TMIE-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at