rs201171064
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_005422.4(TECTA):c.65-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,074 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
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
TECTA
NM_005422.4 splice_polypyrimidine_tract, intron
NM_005422.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.05
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 11-121105817-A-G is Benign according to our data. Variant chr11-121105817-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 179842.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1, Benign=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000105 (16/152294) while in subpopulation EAS AF= 0.0027 (14/5182). AF 95% confidence interval is 0.00163. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.65-14A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000392793.6 | |||
TBCEL-TECTA | NM_001378761.1 | c.1022-14A>G | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.65-14A>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_005422.4 | P4 | |||
TECTA | ENST00000264037.2 | c.65-14A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | P4 | ||||
TECTA | ENST00000642222.1 | c.65-14A>G | splice_polypyrimidine_tract_variant, intron_variant | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000279 AC: 70AN: 251182Hom.: 0 AF XY: 0.000295 AC XY: 40AN XY: 135744
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GnomAD4 exome AF: 0.0000636 AC: 93AN: 1461780Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727182
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
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 | Jun 27, 2014 | Variant classified as Uncertain Significance - Favor Benign. The 65-14A>G varian t in TECTA has not been previously reported in individuals with hearing loss, bu t has been identified in 1/194 of Chinese Han chromosomes by the 1000 Genomes Pr oject (dbSNP rs201171064). Although this variant has been seen in the general po pulation, its frequency is not high enough to rule out a pathogenic role. This v ariant is located in the 3' splice region. Computational tools do not suggest an impact to splicing. However, this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the 65-14A>G v ariant is uncertain, the computational data suggest that it is more likely to be benign. - |
Autosomal recessive nonsyndromic hearing loss 21 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2023 | - - |
Autosomal dominant nonsyndromic hearing loss 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at