11-121168360-A-T

Variant names:

• chr11-121168360-A-T
• rs543577
• NM_005422.4:c.5750+143A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005422.4(TECTA):​c.5750+143A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.5750+143A>T		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.6692+143A>T		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.5750+143A>T		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.5750+143A>T		intron	N/A	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.5735+143A>T		intron	N/A	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 984394 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 509032

African (AFR) AF: 0.00 AC: 0 AN: 23970

American (AMR) AF: 0.00 AC: 0 AN: 41550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22920

East Asian (EAS) AF: 0.00 AC: 0 AN: 37108

South Asian (SAS) AF: 0.00 AC: 0 AN: 74706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 689220

Other (OTH) AF: 0.00 AC: 0 AN: 44650

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152034 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		-0.11

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: rs543577; hg19: chr11-121039069;