rs144441070
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005422.4(TECTA):c.4011G>A(p.Ala1337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,018 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0059 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 11 hom. )
Consequence
TECTA
NM_005422.4 synonymous
NM_005422.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.51
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 11-121146022-G-A is Benign according to our data. Variant chr11-121146022-G-A is described in ClinVar as [Benign]. Clinvar id is 45327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121146022-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-3.51 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (892/152358) while in subpopulation AFR AF= 0.0203 (842/41574). AF 95% confidence interval is 0.0191. There are 10 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.4011G>A | p.Ala1337= | synonymous_variant | 12/24 | ENST00000392793.6 | NP_005413.2 | |
TBCEL-TECTA | NM_001378761.1 | c.4968G>A | p.Ala1656= | synonymous_variant | 18/30 | NP_001365690.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.4011G>A | p.Ala1337= | synonymous_variant | 12/24 | 5 | NM_005422.4 | ENSP00000376543 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00583 AC: 887AN: 152240Hom.: 10 Cov.: 33
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GnomAD3 exomes AF: 0.00136 AC: 340AN: 250144Hom.: 5 AF XY: 0.00105 AC XY: 142AN XY: 135546
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GnomAD4 exome AF: 0.000623 AC: 910AN: 1461660Hom.: 11 Cov.: 31 AF XY: 0.000529 AC XY: 385AN XY: 727138
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GnomAD4 genome AF: 0.00585 AC: 892AN: 152358Hom.: 10 Cov.: 33 AF XY: 0.00561 AC XY: 418AN XY: 74512
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 14, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Ala1337Ala in Exon 11 of TECTA: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 1.8% (68/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs144441070). - |
Computational scores
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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