11-121168360-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005422.4(TECTA):​c.5750+143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,134,490 control chromosomes in the GnomAD database, including 229,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (37568 hom., cov: 32)
  • Exomes 𝑓: 0.62 (192137 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-121168360-A-G is Benign according to our data. Variant chr11-121168360-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 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.5750+143A>G		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.6692+143A>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.5750+143A>G		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.5750+143A>G		intron	N/A	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.5735+143A>G		intron	N/A	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104545 AN: 151994 Hom.: 37522 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.621 AC: 610221 AN: 982378 Hom.: 192137 Cov.: 13 AF XY: 0.625 AC XY: 317580 AN XY: 508036

African (AFR) AF: 0.924 AC: 22144 AN: 23958

American (AMR) AF: 0.528 AC: 21937 AN: 41510

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 13683 AN: 22894

East Asian (EAS) AF: 0.551 AC: 20437 AN: 37080

South Asian (SAS) AF: 0.716 AC: 53443 AN: 74644

European-Finnish (FIN) AF: 0.614 AC: 28843 AN: 46976

Middle Eastern (MID) AF: 0.682 AC: 2188 AN: 3208

European-Non Finnish (NFE) AF: 0.609 AC: 418994 AN: 687516

Other (OTH) AF: 0.640 AC: 28552 AN: 44592

GnomAD4 genome AF: 0.688 AC: 104641 AN: 152112 Hom.: 37568 Cov.: 32 AF XY: 0.683 AC XY: 50828 AN XY: 74374

African (AFR) AF: 0.911 AC: 37855 AN: 41532

American (AMR) AF: 0.582 AC: 8883 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2827 AN: 5178

South Asian (SAS) AF: 0.721 AC: 3480 AN: 4826

European-Finnish (FIN) AF: 0.596 AC: 6286 AN: 10552

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 41172 AN: 67964

Other (OTH) AF: 0.675 AC: 1425 AN: 2110

Alfa AF: 0.641 Hom.: 11494

Bravo AF: 0.692

Asia WGS AF: 0.632 AC: 2199 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.47
PhyloP100		-0.11
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: rs543577; hg19: chr11-121039069; COSMIC: COSV50722911;