11-121125534-C-T

Variant names:

• chr11-121125534-C-T
• rs35107075
• NM_005422.4:c.1436C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.1436C>T (p.Pro479Leu) variant in the TECTA gene is 0.63% (219/30782) of South Asian 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 recessive hearing loss variants (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA182711/MONDO:0019497/005

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 34)
  • Exomes 𝑓: 0.00073 (4 hom.)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Benign reviewed by expert panel U:1 B:7
• Conservation: PhyloP100: 1.96
• Publications: 8 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: For more information check the summary or visit ClinGen Evidence Repository.

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.1436C>T	p.Pro479Leu	missense	Exon 8 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.2393C>T	p.Pro798Leu	missense	Exon 14 of 30	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.1436C>T	p.Pro479Leu	missense	Exon 8 of 24	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.1436C>T	p.Pro479Leu	missense	Exon 7 of 23	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.1436C>T	p.Pro479Leu	missense	Exon 8 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 301 AN: 152206 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00577

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00144 AC: 362 AN: 251350 AF XY: 0.00165

Gnomad AFR exome AF: 0.00621

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000735 AC: 1074 AN: 1461838 Hom.: 4 Cov.: 31 AF XY: 0.000923 AC XY: 671 AN XY: 727216

African (AFR) AF: 0.00729 AC: 244 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00683 AC: 589 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000124 AC: 138 AN: 1112010

Other (OTH) AF: 0.000960 AC: 58 AN: 60396

GnomAD4 genome AF: 0.00198 AC: 301 AN: 152324 Hom.: 2 Cov.: 34 AF XY: 0.00204 AC XY: 152 AN XY: 74492

African (AFR) AF: 0.00575 AC: 239 AN: 41568

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000852 Hom.: 0

Bravo AF: 0.00208

ESP6500AA AF: 0.00522 AC: 23

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00161 AC: 195

EpiCase AF: 0.0000545

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal dominant nonsyndromic hearing loss 12 (1)
-	1	-	Autosomal recessive nonsyndromic hearing loss 21 (1)
-	-	1	Nonsyndromic genetic hearing loss (1)
-	-	1	not specified (1)
-	-	1	TECTA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N
PhyloP100		2.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.037
Sift	Benign	0.41	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.15
MVP		0.57
MPC		0.33
ClinPred		0.014	T
GERP RS		5.0
Varity_R		0.092
gMVP		0.66
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs35107075; hg19: chr11-120996243;