11-121102694-G-C

Position:

• chr11-121102694-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_005422.4(TECTA):​c.29G>C​(p.Trp10Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.59

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-121102694-G-C is Benign according to our data. Variant chr11-121102694-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 689604.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.29G>C	p.Trp10Ser	missense_variant	2/24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.986G>C	p.Trp329Ser	missense_variant	8/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.29G>C	p.Trp10Ser	missense_variant	2/24	5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.938G>C	p.Trp313Ser	missense_variant	7/10			ENSP00000496315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461478 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 12 Benign:1

Likely benign, criteria provided, single submitter

case-control

Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;T;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;.;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	.;L;.;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.27	.;N;.;N
REVEL	Benign	0.19
Sift	Uncertain	0.021	.;D;.;D
Sift4G	Uncertain	0.024	.;D;.;D
Polyphen		0.60	.;P;.;P
Vest4		0.60, 0.63
MutPred		0.68		.;Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);Gain of disorder (P = 0.0032);
MVP		0.51
MPC		0.52
ClinPred		0.48	T
GERP RS		5.2
Varity_R		0.15
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs1591433475; hg19: chr11-120973403;