11-121102807-C-T

Variant names:

• chr11-121102807-C-T
• rs56358414
• NM_005422.4:c.64+78C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005422.4(TECTA):​c.64+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,230,138 control chromosomes in the GnomAD database, including 525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (269 hom., cov: 32)
  • Exomes 𝑓: 0.012 (256 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-121102807-C-T is Benign according to our data. Variant chr11-121102807-C-T is described in ClinVar as [Benign]. Clinvar id is 1283274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.64+78C>T		intron_variant	Intron 2 of 23	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.1021+78C>T		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.64+78C>T		intron_variant	Intron 2 of 23	5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.973+78C>T		intron_variant	Intron 7 of 9			ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5698 AN: 152070 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0121 AC: 13072 AN: 1077950 Hom.: 256 AF XY: 0.0130 AC XY: 7192 AN XY: 553496

African (AFR) AF: 0.109 AC: 2802 AN: 25682

American (AMR) AF: 0.0108 AC: 474 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 405 AN: 23750

East Asian (EAS) AF: 0.000105 AC: 4 AN: 37936

South Asian (SAS) AF: 0.0291 AC: 2255 AN: 77622

European-Finnish (FIN) AF: 0.000602 AC: 32 AN: 53166

Middle Eastern (MID) AF: 0.0393 AC: 197 AN: 5010

European-Non Finnish (NFE) AF: 0.00796 AC: 6076 AN: 763178

Other (OTH) AF: 0.0174 AC: 827 AN: 47652

GnomAD4 genome AF: 0.0376 AC: 5716 AN: 152188 Hom.: 269 Cov.: 32 AF XY: 0.0364 AC XY: 2712 AN XY: 74408

African (AFR) AF: 0.109 AC: 4521 AN: 41482

American (AMR) AF: 0.0178 AC: 272 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4824

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00890 AC: 605 AN: 68012

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0282 Hom.: 24

Bravo AF: 0.0427

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 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	-0.72
CADD	Benign	15
DANN	Benign	0.57
PhyloP100		1.1
PromoterAI		0.0030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs56358414; hg19: chr11-120973516;