chr11-121113220-C-G

Variant names:

• chr11-121113220-C-G
• rs73599492
• NM_005422.4:c.624+11C>G

Variant summary

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

The NM_001378761.1(TBCEL-TECTA):​c.1581+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,613,902 control chromosomes in the GnomAD database, including 597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (307 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (290 hom.)
• Consequence: TBCEL-TECTA NM_001378761.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.417
• Publications: 4 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=-0.73).
• BP6: Variant 11-121113220-C-G is Benign according to our data. Variant chr11-121113220-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378761.1. 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.624+11C>G		intron	N/A	NP_005413.2
	TBCEL-TECTA	NM_001378761.1		c.1581+11C>G		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.624+11C>G		intron	N/A	ENSP00000376543.1
	TECTA	ENST00000264037.2	TSL:1	c.624+11C>G		intron	N/A	ENSP00000264037.2
	TECTA	ENST00000642222.1		c.624+11C>G		intron	N/A	ENSP00000493855.1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5305 AN: 152062 Hom.: 308 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.00892 AC: 2236 AN: 250768 AF XY: 0.00633

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00535

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000530

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00371 AC: 5430 AN: 1461722 Hom.: 290 Cov.: 32 AF XY: 0.00314 AC XY: 2285 AN XY: 727164

African (AFR) AF: 0.126 AC: 4205 AN: 33480

American (AMR) AF: 0.00606 AC: 271 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00329 AC: 86 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5768

European-Non Finnish (NFE) AF: 0.000290 AC: 322 AN: 1112012

Other (OTH) AF: 0.00798 AC: 482 AN: 60394

GnomAD4 genome AF: 0.0350 AC: 5319 AN: 152180 Hom.: 307 Cov.: 32 AF XY: 0.0343 AC XY: 2554 AN XY: 74404

African (AFR) AF: 0.119 AC: 4947 AN: 41496

American (AMR) AF: 0.0164 AC: 251 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

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

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68002

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.00537 Hom.: 3

Bravo AF: 0.0399

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Autosomal dominant nonsyndromic hearing loss 12 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 21 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		-0.42
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: rs73599492; hg19: chr11-120983929;