11-121105751-G-A

Variant names:

• chr11-121105751-G-A
• rs114256496
• NM_005422.4:c.65-80G>A

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.65-80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,583,210 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (47 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.760
• Publications: 0 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=-0.81).
• BP6: Variant 11-121105751-G-A is Benign according to our data. Variant chr11-121105751-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1196730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1997/152302) while in subpopulation AFR AF = 0.0453 (1882/41548). AF 95% confidence interval is 0.0436. There are 53 homozygotes in GnomAd4. There are 960 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005422.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.65-80G>A		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.1022-80G>A		intron	N/A	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.65-80G>A		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.65-80G>A		intron	N/A	ENSP00000264037.2	O75443
	TBCEL-TECTA	ENST00000645041.1		c.974-80G>A		intron	N/A	ENSP00000496315.1	A0A2R8YFB7

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1992 AN: 152184 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00129 AC: 1846 AN: 1430908 Hom.: 47 AF XY: 0.00108 AC XY: 772 AN XY: 711588

African (AFR) AF: 0.0456 AC: 1506 AN: 33008

American (AMR) AF: 0.00244 AC: 103 AN: 42252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25832

East Asian (EAS) AF: 0.00 AC: 0 AN: 39234

South Asian (SAS) AF: 0.0000949 AC: 8 AN: 84312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49366

Middle Eastern (MID) AF: 0.00176 AC: 9 AN: 5110

European-Non Finnish (NFE) AF: 0.0000394 AC: 43 AN: 1092336

Other (OTH) AF: 0.00298 AC: 177 AN: 59458

GnomAD4 genome AF: 0.0131 AC: 1997 AN: 152302 Hom.: 53 Cov.: 32 AF XY: 0.0129 AC XY: 960 AN XY: 74480

African (AFR) AF: 0.0453 AC: 1882 AN: 41548

American (AMR) AF: 0.00568 AC: 87 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00367 Hom.: 1

Bravo AF: 0.0145

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.59
PhyloP100		0.76
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: rs114256496; hg19: chr11-120976460;