rs141488594
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_005422.4(TECTA):āc.1320T>Cā(p.Asp440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,238 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00013 ( 0 hom., cov: 34)
Exomes š: 0.000012 ( 0 hom. )
Consequence
TECTA
NM_005422.4 synonymous
NM_005422.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.46
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 -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 11-121125418-T-C is Benign according to our data. Variant chr11-121125418-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 178534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.46 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.1320T>C | p.Asp440= | synonymous_variant | 8/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.2277T>C | p.Asp759= | synonymous_variant | 14/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.1320T>C | p.Asp440= | synonymous_variant | 8/24 | 5 | NM_005422.4 | P4 | |
TECTA | ENST00000264037.2 | c.1320T>C | p.Asp440= | synonymous_variant | 7/23 | 1 | P4 | ||
TECTA | ENST00000642222.1 | c.1320T>C | p.Asp440= | synonymous_variant | 8/24 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152254Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251470Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135910
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461866Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727236
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152372Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74520
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Asp440Asp in Exon 07 of TECTA: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1/3738 African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs141488594). - |
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