11-121102587-A-C

Variant names:

• chr11-121102587-A-C
• rs56058285
• NM_005422.4:c.-1-78A>C

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.-1-78A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,047,042 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (270 hom., cov: 32)
  • Exomes 𝑓: 0.013 (248 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500
• Publications: 3 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=-0.65).
• BP6: Variant 11-121102587-A-C is Benign according to our data. Variant chr11-121102587-A-C is described in ClinVar as [Benign]. Clinvar id is 1244654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.-1-78A>C		intron_variant	Intron 1 of 23	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.957-78A>C		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.-1-78A>C		intron_variant	Intron 1 of 23	5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.909-78A>C		intron_variant	Intron 6 of 9			ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5710 AN: 152142 Hom.: 269 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: 0.0307

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0310

GnomAD4 exome AF: 0.0131 AC: 11740 AN: 894782 Hom.: 248 AF XY: 0.0139 AC XY: 6498 AN XY: 468420

African (AFR) AF: 0.114 AC: 2564 AN: 22460

American (AMR) AF: 0.0109 AC: 473 AN: 43306

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 406 AN: 22620

East Asian (EAS) AF: 0.000108 AC: 4 AN: 36968

South Asian (SAS) AF: 0.0296 AC: 2201 AN: 74358

European-Finnish (FIN) AF: 0.000615 AC: 32 AN: 51994

Middle Eastern (MID) AF: 0.0374 AC: 137 AN: 3662

European-Non Finnish (NFE) AF: 0.00865 AC: 5173 AN: 597856

Other (OTH) AF: 0.0180 AC: 750 AN: 41558

GnomAD4 genome AF: 0.0376 AC: 5728 AN: 152260 Hom.: 270 Cov.: 32 AF XY: 0.0364 AC XY: 2713 AN XY: 74454

African (AFR) AF: 0.109 AC: 4536 AN: 41530

American (AMR) AF: 0.0178 AC: 272 AN: 15296

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

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

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4820

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00889 AC: 605 AN: 68022

Other (OTH) AF: 0.0307 AC: 65 AN: 2116

Alfa AF: 0.0285 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	-0.65
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		0.050
PromoterAI		0.012	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: rs56058285; hg19: chr11-120973296;