3-46709583-TAAGAAGAAGAAGAAG-TAAGAAGAAGAAGAAGAAGAAGAAG
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_147196.3(TMIE):c.385_393dupAAGAAGAAG(p.Lys129_Lys131dup) variant causes a conservative inframe insertion 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 0.000013 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000064 ( 0 hom. )
Consequence
TMIE
NM_147196.3 conservative_inframe_insertion
NM_147196.3 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.773
Publications
21 publications found
Genes affected
TMIE (HGNC:30800): (transmembrane inner ear) This gene encodes a transmembrane inner ear protein. Studies in mouse suggest that this gene is required for normal postnatal maturation of sensory hair cells in the cochlea, including correct development of stereocilia bundles. This gene is one of multiple genes responsible for recessive non-syndromic deafness (DFNB), also known as autosomal recessive nonsyndromic hearing loss (ARNSHL), the most common form of congenitally acquired inherited hearing impairment. [provided by RefSeq, Mar 2009]
TMIE Gene-Disease associations (from GenCC):
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive nonsyndromic hearing loss 6Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_147196.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_147196.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TMIE | MANE Select | c.385_393dupAAGAAGAAG | p.Lys129_Lys131dup | conservative_inframe_insertion | Exon 4 of 4 | NP_671729.2 | Q8NEW7 | ||
| TMIE | c.226_234dupAAGAAGAAG | p.Lys76_Lys78dup | conservative_inframe_insertion | Exon 4 of 4 | NP_001357453.1 | A0A2R8YDZ8 | |||
| TMIE | c.226_234dupAAGAAGAAG | p.Lys76_Lys78dup | conservative_inframe_insertion | Exon 5 of 5 | NP_001357454.1 | A0A2R8YDZ8 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TMIE | MANE Select | c.385_393dupAAGAAGAAG | p.Lys129_Lys131dup | conservative_inframe_insertion | Exon 4 of 4 | ENSP00000494576.2 | Q8NEW7 | ||
| TMIE | c.226_234dupAAGAAGAAG | p.Lys76_Lys78dup | conservative_inframe_insertion | Exon 4 of 4 | ENSP00000495111.1 | A0A2R8YDZ8 | |||
| TMIE | c.*307_*315dupAAGAAGAAG | 3_prime_UTR | Exon 2 of 2 | ENSP00000498953.1 | A0A494C1A3 |
Frequencies
GnomAD3 genomes 0.0000133 AC: 2AN: 149948Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
149948
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000642 AC: 9AN: 1402590Hom.: 0 Cov.: 0 AF XY: 0.00000858 AC XY: 6AN XY: 698902 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
9
AN:
1402590
Hom.:
Cov.:
0
AF XY:
AC XY:
6
AN XY:
698902
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
31790
American (AMR)
AF:
AC:
0
AN:
43630
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25346
East Asian (EAS)
AF:
AC:
1
AN:
38820
South Asian (SAS)
AF:
AC:
0
AN:
84782
European-Finnish (FIN)
AF:
AC:
0
AN:
51750
Middle Eastern (MID)
AF:
AC:
0
AN:
5628
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1062742
Other (OTH)
AF:
AC:
1
AN:
58102
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000656608), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.364
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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6
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30-35
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>80
Age
GnomAD4 genome 0.0000133 AC: 2AN: 149948Hom.: 0 Cov.: 0 AF XY: 0.0000137 AC XY: 1AN XY: 73004 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
149948
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
73004
show subpopulations
African (AFR)
AF:
AC:
2
AN:
40688
American (AMR)
AF:
AC:
0
AN:
15042
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3452
East Asian (EAS)
AF:
AC:
0
AN:
5076
South Asian (SAS)
AF:
AC:
0
AN:
4724
European-Finnish (FIN)
AF:
AC:
0
AN:
10192
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67492
Other (OTH)
AF:
AC:
0
AN:
2068
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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