chr11-121164909-T-C

Variant names:

• chr11-121164909-T-C
• rs549507
• NM_005422.4:c.5273-364T>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.5273-364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,108 control chromosomes in the GnomAD database, including 37,748 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 0.69 (37748 hom., cov: 32)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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.5273-364T>C		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.6215-364T>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.5273-364T>C		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.5273-364T>C		intron	N/A	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.5258-364T>C		intron	N/A	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104943 AN: 151990 Hom.: 37702 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 105040 AN: 152108 Hom.: 37748 Cov.: 32 AF XY: 0.687 AC XY: 51072 AN XY: 74346

African (AFR) AF: 0.908 AC: 37704 AN: 41518

American (AMR) AF: 0.616 AC: 9406 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2027 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2858 AN: 5156

South Asian (SAS) AF: 0.721 AC: 3474 AN: 4818

European-Finnish (FIN) AF: 0.596 AC: 6301 AN: 10564

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41146 AN: 67984

Other (OTH) AF: 0.681 AC: 1438 AN: 2112

Alfa AF: 0.654 Hom.: 20329

Bravo AF: 0.698

Asia WGS AF: 0.636 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.42
PhyloP100		-1.2
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: rs549507; hg19: chr11-121035618;