rs612969
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005422.4(TECTA):c.1111A>G(p.Arg371Gly) variant causes a missense change. The variant allele was found at a frequency of 0.423 in 1,613,798 control chromosomes in the GnomAD database, including 149,284 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.48 ( 18608 hom., cov: 31)
Exomes 𝑓: 0.42 ( 130676 hom. )
Consequence
TECTA
NM_005422.4 missense
NM_005422.4 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 4.96
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=3.4409682E-6).
BP6
?
Variant 11-121118626-A-G is Benign according to our data. Variant chr11-121118626-A-G is described in ClinVar as [Benign]. Clinvar id is 45314.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr11-121118626-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.1111A>G | p.Arg371Gly | missense_variant | 7/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.2068A>G | p.Arg690Gly | missense_variant | 13/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.1111A>G | p.Arg371Gly | missense_variant | 7/24 | 5 | NM_005422.4 | P4 | |
TECTA | ENST00000264037.2 | c.1111A>G | p.Arg371Gly | missense_variant | 6/23 | 1 | P4 | ||
TECTA | ENST00000642222.1 | c.1111A>G | p.Arg371Gly | missense_variant | 7/24 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.475 AC: 72144AN: 151848Hom.: 18595 Cov.: 31
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GnomAD3 exomes AF: 0.398 AC: 99962AN: 251444Hom.: 21085 AF XY: 0.391 AC XY: 53154AN XY: 135894
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GnomAD4 exome AF: 0.418 AC: 610985AN: 1461832Hom.: 130676 Cov.: 63 AF XY: 0.413 AC XY: 300683AN XY: 727218
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GnomAD4 genome ? AF: 0.475 AC: 72204AN: 151966Hom.: 18608 Cov.: 31 AF XY: 0.468 AC XY: 34752AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Arg371Gly in Exon 06 of TECTA: This variant is not expected to have clinical sig nificance because it has been identified in 41.0% (2877/7020) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs612969). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive nonsyndromic hearing loss 21 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Autosomal dominant nonsyndromic hearing loss 12 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Nonsyndromic genetic hearing loss Benign:1
Benign, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | Sep 28, 2018 | The filtering allele frequency of the p.Arg317Gly variant in the TECTA gene is 67.5% (16434/24006) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant and autosomal recessive hearing loss variants (BA1). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;.;T
Polyphen
B;.;B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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