chr3-46705866-G-A
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_147196.3(TMIE):c.170G>A(p.Trp57*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TMIE
NM_147196.3 stop_gained
NM_147196.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 8.33
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-46705866-G-A is Pathogenic according to our data. Variant chr3-46705866-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3394.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-46705866-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMIE | NM_147196.3 | c.170G>A | p.Trp57* | stop_gained | Exon 2 of 4 | ENST00000643606.3 | NP_671729.2 | |
TMIE | NM_001370524.1 | c.11G>A | p.Trp4* | stop_gained | Exon 2 of 4 | NP_001357453.1 | ||
TMIE | NM_001370525.1 | c.11G>A | p.Trp4* | stop_gained | Exon 3 of 5 | NP_001357454.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMIE | ENST00000643606.3 | c.170G>A | p.Trp57* | stop_gained | Exon 2 of 4 | NM_147196.3 | ENSP00000494576.2 | |||
TMIE | ENST00000644830.1 | c.11G>A | p.Trp4* | stop_gained | Exon 2 of 4 | ENSP00000495111.1 | ||||
TMIE | ENST00000651652.1 | c.68G>A | p.Trp23* | stop_gained | Exon 1 of 2 | ENSP00000498953.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461820Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727222
GnomAD4 exome
AF:
AC:
1
AN:
1461820
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727222
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 6 Pathogenic:1
Jun 01, 2009
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
0.80
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at