11-121102565-C-T

Variant names:

• chr11-121102565-C-T
• rs79614045
• NM_005422.4:c.-1-100C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005422.4(TECTA):​c.-1-100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 880,136 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 32)
  • Exomes 𝑓: 0.012 (129 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.181
• Publications: 5 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=-0.5).
• BP6: Variant 11-121102565-C-T is Benign according to our data. Variant chr11-121102565-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1209193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00774 (1179/152272) while in subpopulation SAS AF = 0.033 (159/4824). AF 95% confidence interval is 0.0288. There are 6 homozygotes in GnomAd4. There are 586 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.-1-100C>T		intron_variant	Intron 1 of 23	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.957-100C>T		intron_variant	Intron 7 of 29		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.-1-100C>T		intron_variant	Intron 1 of 23	5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.909-100C>T		intron_variant	Intron 6 of 9			ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.00778 AC: 1184 AN: 152154 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0122 AC: 8862 AN: 727864 Hom.: 129 AF XY: 0.0136 AC XY: 5306 AN XY: 388812

African (AFR) AF: 0.00126 AC: 24 AN: 19000

American (AMR) AF: 0.00506 AC: 205 AN: 40540

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 385 AN: 21300

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35790

South Asian (SAS) AF: 0.0343 AC: 2391 AN: 69682

European-Finnish (FIN) AF: 0.00457 AC: 228 AN: 49924

Middle Eastern (MID) AF: 0.0212 AC: 62 AN: 2920

European-Non Finnish (NFE) AF: 0.0113 AC: 5134 AN: 452780

Other (OTH) AF: 0.0120 AC: 432 AN: 35928

GnomAD4 genome AF: 0.00774 AC: 1179 AN: 152272 Hom.: 6 Cov.: 32 AF XY: 0.00787 AC XY: 586 AN XY: 74454

African (AFR) AF: 0.00173 AC: 72 AN: 41572

American (AMR) AF: 0.00562 AC: 86 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3462

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4824

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 729 AN: 68020

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.0110 Hom.: 4

Bravo AF: 0.00711

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 25, 2019

GeneDx

Significance: Likely 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	-0.50
CADD	Benign	6.4
DANN	Benign	0.67
PhyloP100		0.18
PromoterAI		-0.0046	Neutral
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: rs79614045; hg19: chr11-120973274;