rs876657371
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP3PP5
The NM_147196.3(TMIE):c.94-2_98delinsC variant causes a splice acceptor, coding sequence change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
TMIE
NM_147196.3 splice_acceptor, coding_sequence
NM_147196.3 splice_acceptor, coding_sequence
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.29
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 3-46705788-AGCCCAG-C is Pathogenic according to our data. Variant chr3-46705788-AGCCCAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 3393.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMIE | NM_147196.3 | c.94-2_98delinsC | splice_acceptor_variant, coding_sequence_variant | 2/4 | ENST00000643606.3 | ||
TMIE | NM_001370524.1 | c.-66-2_-62delinsC | splice_acceptor_variant, 5_prime_UTR_variant | 2/4 | |||
TMIE | NM_001370525.1 | c.-66-2_-62delinsC | splice_acceptor_variant, 5_prime_UTR_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMIE | ENST00000643606.3 | c.94-2_98delinsC | splice_acceptor_variant, coding_sequence_variant | 2/4 | NM_147196.3 | P1 | |||
TMIE | ENST00000644830.1 | c.-66-2_-62delinsC | splice_acceptor_variant, 5_prime_UTR_variant | 2/4 | |||||
TMIE | ENST00000651652.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at