Genetic Variant TECTA:c.5273-364T>C (chr11-121164909-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005422.4(TECTA):c.5273-364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,108 control chromosomes in the GnomAD database, including 37,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 37748 hom., cov: 32)

Consequence

TECTA
NM_005422.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

2 publications found

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]

TECTA links:

TBCEL-TECTA (HGNC:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.5273-364T>C		intron_variant	Intron 16 of 23	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.6215-364T>C		intron_variant	Intron 22 of 29		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 link	c.5273-364T>C		intron_variant	Intron 16 of 23	5	NM_005422.4	ENSP00000376543.1		O75443

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

104943

AN:

151990

Hom.:

37702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.908

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.691

AC:

105040

AN:

152108

Hom.:

37748

Cov.:

AF XY:

0.687

AC XY:

51072

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.908

AC:

37704

AN:

41518

American (AMR)

AF:

0.616

AC:

9406

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

2027

AN:

3472

East Asian (EAS)

AF:

0.554

AC:

2858

AN:

5156

South Asian (SAS)

AF:

0.721

AC:

3474

AN:

4818

European-Finnish (FIN)

AF:

0.596

AC:

6301

AN:

10564

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41146

AN:

67984

Other (OTH)

AF:

0.681

AC:

1438

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1570

3139

4709

6278

7848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.654

Hom.:

20329

Bravo

AF:

0.698

Asia WGS

AF:

0.636

AC:

2213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.25

(source)

DANN

Benign

0.42

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over