11-121105602-A-C

Variant names:

• chr11-121105602-A-C
• rs55683640
• NM_005422.4:c.65-229A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005422.4(TECTA):​c.65-229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 152,352 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (189 hom., cov: 32)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.484
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-121105602-A-C is Benign according to our data. Variant chr11-121105602-A-C is described in ClinVar as [Benign]. Clinvar id is 1229784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.65-229A>C		intron_variant	Intron 2 of 23	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.1022-229A>C		intron_variant	Intron 8 of 29		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.65-229A>C		intron_variant	Intron 2 of 23	5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.974-229A>C		intron_variant	Intron 7 of 9			ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6561 AN: 152234 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0431 AC: 6563 AN: 152352 Hom.: 189 Cov.: 32 AF XY: 0.0423 AC XY: 3149 AN XY: 74508

African (AFR) AF: 0.0119 AC: 496 AN: 41592

American (AMR) AF: 0.0393 AC: 601 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4832

European-Finnish (FIN) AF: 0.0581 AC: 617 AN: 10624

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4525 AN: 68012

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0572 Hom.: 51

Bravo AF: 0.0413

Asia WGS AF: 0.00779 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.58
PhyloP100		-0.48
Mutation Taster		=100/0	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: rs55683640; hg19: chr11-120976311;