dbSNP rs142903119: TECTA:p.His927His (chr11-121130051-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_005422.4(TECTA):c.2781T>C(p.His927His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,613,996 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). The gene TECTA is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 25 hom. )

Consequence

TECTA
NM_005422.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.290

Publications

1 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

Specifications for TECTA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-121130051-T-C is Benign according to our data. Variant chr11-121130051-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 178636.

BP7

Synonymous conserved (PhyloP=-0.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00389 (592/152266) while in subpopulation NFE AF = 0.00528 (359/68016). AF 95% confidence interval is 0.00483. There are 1 homozygotes in GnomAd4. There are 285 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 25 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005422.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.2781T>C	p.His927His	synonymous	Exon 10 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.3738T>C	p.His1246His	synonymous	Exon 16 of 30	NP_001365690.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TECTA	ENST00000392793.6	TSL:5 MANE Select	c.2781T>C	p.His927His	synonymous	Exon 10 of 24	ENSP00000376543.1	O75443
TECTA	ENST00000264037.2	TSL:1	c.2781T>C	p.His927His	synonymous	Exon 9 of 23	ENSP00000264037.2	O75443
TECTA	ENST00000642222.1		c.2781T>C	p.His927His	synonymous	Exon 10 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

591

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00528

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00417

AC:

1048

AN:

251094

AF XY:

0.00422

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00474

AC:

6930

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

3350

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33478

American (AMR)

AF:

0.000872

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00582

AC:

152

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00179

AC:

154

AN:

86234

European-Finnish (FIN)

AF:

0.0131

AC:

699

AN:

53388

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00500

AC:

5555

AN:

1111932

Other (OTH)

AF:

0.00512

AC:

309

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

465

930

1395

1860

2325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00389

AC:

592

AN:

152266

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000987

AC:

AN:

41546

American (AMR)

AF:

0.00111

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00228

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00528

AC:

359

AN:

68016

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00453

Hom.:

Bravo

AF:

0.00286

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00367

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal dominant nonsyndromic hearing loss 12 (1)

Autosomal recessive nonsyndromic hearing loss 21 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.36

PhyloP100

-0.29

PromoterAI

0.058

Neutral

(source)

Mutation Taster

=86/14

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over