rs1184726805
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005422.4(TECTA):āc.3440A>Gā(p.Asn1147Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
TECTA
NM_005422.4 missense
NM_005422.4 missense
Scores
10
8
Clinical Significance
Conservation
PhyloP100: 5.29
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.3440A>G | p.Asn1147Ser | missense_variant | 11/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.4397A>G | p.Asn1466Ser | missense_variant | 17/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.3440A>G | p.Asn1147Ser | missense_variant | 11/24 | 5 | NM_005422.4 | P4 | |
TECTA | ENST00000264037.2 | c.3440A>G | p.Asn1147Ser | missense_variant | 10/23 | 1 | P4 | ||
TECTA | ENST00000642222.1 | c.3440A>G | p.Asn1147Ser | missense_variant | 11/24 | A1 | |||
TECTA | ENST00000645008.1 | c.749A>G | p.Asn250Ser | missense_variant | 2/15 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451908Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 719892
GnomAD4 exome
AF:
AC:
2
AN:
1451908
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
719892
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
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 | Mar 16, 2017 | The p.Asn1147Ser variant in TECTA has not been previously reported in individual s with hearing loss or in large population studies. Splice prediction tools indi cate the possible creation of a cryptic splice site; however, this information i s not predictive enough to determine pathogenicity. Additional computational pr ediction tools and conservation analysis do not provide strong support for or ag ainst an impact to the protein. In summary, the clinical significance of the p.A sn1147Ser variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Benign
T;.;T
Polyphen
B;.;B
Vest4
MutPred
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at