rs586473

Variant names:

• chr11-121130075-T-C
• rs586473
• NM_005422.4:c.2805T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-121130075-T-C
• chr11-121130075-T-A

Variant summary

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

The NM_005422.4(TECTA):​c.2805T>C​(p.Tyr935Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.702 in 1,613,820 control chromosomes in the GnomAD database, including 399,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene TECTA is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.74 (41683 hom., cov: 32)
  • Exomes 𝑓: 0.70 (357673 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 4.09
• Publications: 30 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

Specifications for TECTA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-121130075-T-C is Benign according to our data. Variant chr11-121130075-T-C is described in ClinVar as Benign. ClinVar VariationId is 45323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 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.2805T>C	p.Tyr935Tyr	synonymous	Exon 10 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.3762T>C	p.Tyr1254Tyr	synonymous	Exon 16 of 30	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.2805T>C	p.Tyr935Tyr	synonymous	Exon 10 of 24	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.2805T>C	p.Tyr935Tyr	synonymous	Exon 9 of 23	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.2805T>C	p.Tyr935Tyr	synonymous	Exon 10 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111771 AN: 151972 Hom.: 41644 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.732

GnomAD2 exomes AF: 0.697 AC: 174979 AN: 251196 AF XY: 0.698

Gnomad AFR exome AF: 0.869

Gnomad AMR exome AF: 0.612

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.675

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.700

GnomAD4 exome AF: 0.698 AC: 1020545 AN: 1461730 Hom.: 357673 Cov.: 87 AF XY: 0.699 AC XY: 508448 AN XY: 727152

African (AFR) AF: 0.875 AC: 29288 AN: 33480

American (AMR) AF: 0.617 AC: 27593 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 16226 AN: 26136

East Asian (EAS) AF: 0.684 AC: 27170 AN: 39700

South Asian (SAS) AF: 0.721 AC: 62174 AN: 86254

European-Finnish (FIN) AF: 0.735 AC: 39148 AN: 53286

Middle Eastern (MID) AF: 0.699 AC: 4030 AN: 5768

European-Non Finnish (NFE) AF: 0.695 AC: 772497 AN: 1111988

Other (OTH) AF: 0.702 AC: 42419 AN: 60394

GnomAD4 genome AF: 0.735 AC: 111857 AN: 152090 Hom.: 41683 Cov.: 32 AF XY: 0.735 AC XY: 54653 AN XY: 74326

African (AFR) AF: 0.864 AC: 35887 AN: 41524

American (AMR) AF: 0.660 AC: 10088 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3487 AN: 5162

South Asian (SAS) AF: 0.733 AC: 3535 AN: 4820

European-Finnish (FIN) AF: 0.722 AC: 7629 AN: 10562

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46803 AN: 67946

Other (OTH) AF: 0.730 AC: 1539 AN: 2108

Alfa AF: 0.702 Hom.: 56604

Bravo AF: 0.734

Asia WGS AF: 0.722 AC: 2511 AN: 3478

EpiCase AF: 0.686

EpiControl AF: 0.686

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 12 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 21 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.58
PhyloP100		4.1
PromoterAI		-0.018	Neutral
Mutation Taster		=94/6	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: rs586473; hg19: chr11-121000784; COSMIC: COSV50691860;