rs1555123919
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_005422.4(TECTA):c.1917_1937dup(p.Ser640_Pro646dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TECTA
NM_005422.4 inframe_insertion
NM_005422.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.909
Genes affected
TECTA (HGNC:11720): (tectorin alpha) The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_005422.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.1917_1937dup | p.Ser640_Pro646dup | inframe_insertion | 9/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.2874_2894dup | p.Ser959_Pro965dup | inframe_insertion | 15/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.1917_1937dup | p.Ser640_Pro646dup | inframe_insertion | 9/24 | 5 | NM_005422.4 | P4 | |
TECTA | ENST00000264037.2 | c.1917_1937dup | p.Ser640_Pro646dup | inframe_insertion | 8/23 | 1 | P4 | ||
TECTA | ENST00000642222.1 | c.1917_1937dup | p.Ser640_Pro646dup | inframe_insertion | 9/24 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 25, 2018 | The p.Ser640_Pro646dup variant in TECTA has been reported by our laboratory in 1 individual with congenital hearing loss and segregated in 1 affected sibling. T his variant was absent from large population studies, though the ability of thes e studies to accurately detect large indels of this size may be limited. This va riant is a tandem duplication of 7 amino acids at positions 640 to 646 and is no t predicted to alter the protein reading-frame. This region of the protein is co nserved across mammalian species, though it is unclear if this duplication will impact protein function. In summary, the clinical significance of the p.Ser640_P ro646dup variant is uncertain. ACMG/AMP criteria applied: PM4. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at