11-121110699-T-C

Variant names:

• chr11-121110699-T-C
• rs1829
• NM_005422.4:c.486+1201T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005422.4(TECTA):​c.486+1201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,144 control chromosomes in the GnomAD database, including 42,601 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (42601 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

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.486+1201T>C		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.1443+1201T>C		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.486+1201T>C		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.486+1201T>C		intron	N/A	ENSP00000264037.2	O75443
	TBCEL-TECTA	ENST00000645041.1		c.1395+1201T>C		intron	N/A	ENSP00000496315.1	A0A2R8YFB7

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113311 AN: 152022 Hom.: 42569 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.745 AC: 113399 AN: 152140 Hom.: 42601 Cov.: 32 AF XY: 0.744 AC XY: 55351 AN XY: 74380

African (AFR) AF: 0.683 AC: 28322 AN: 41484

American (AMR) AF: 0.770 AC: 11776 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2751 AN: 3472

East Asian (EAS) AF: 0.625 AC: 3224 AN: 5160

South Asian (SAS) AF: 0.640 AC: 3080 AN: 4812

European-Finnish (FIN) AF: 0.826 AC: 8750 AN: 10588

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 53191 AN: 68012

Other (OTH) AF: 0.724 AC: 1530 AN: 2112

Alfa AF: 0.766 Hom.: 73198

Bravo AF: 0.744

Asia WGS AF: 0.613 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		0.023
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: rs1829; hg19: chr11-120981408;