rs144441070

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.51
Variant links:
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
TECTANM_005422.4 linkuse as main transcriptc.4011G>A p.Ala1337= synonymous_variant 12/24 ENST00000392793.6 NP_005413.2
TBCEL-TECTANM_001378761.1 linkuse as main transcriptc.4968G>A p.Ala1656= synonymous_variant 18/30 NP_001365690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TECTAENST00000392793.6 linkuse as main transcriptc.4011G>A p.Ala1337= synonymous_variant 12/245 NM_005422.4 ENSP00000376543 P4

Frequencies

GnomAD3 genomes
AF:
0.00583
AC:
887
AN:
152240
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0202
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00255
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00136
AC:
340
AN:
250144
Hom.:
5
AF XY:
0.00105
AC XY:
142
AN XY:
135546
show subpopulations
Gnomad AFR exome
AF:
0.0192
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000623
AC:
910
AN:
1461660
Hom.:
11
Cov.:
31
AF XY:
0.000529
AC XY:
385
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0218
Gnomad4 AMR exome
AF:
0.000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00132
GnomAD4 genome
AF:
0.00585
AC:
892
AN:
152358
Hom.:
10
Cov.:
33
AF XY:
0.00561
AC XY:
418
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0203
Gnomad4 AMR
AF:
0.00255
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00209
Hom.:
3
Bravo
AF:
0.00678
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 15, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 14, 2019- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineApr 30, 2012Ala1337Ala 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.21
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144441070; hg19: chr11-121016731; COSMIC: COSV50749983; COSMIC: COSV50749983; API