rs536069

Variant names:

• chr11-121125583-A-G
• rs536069
• NM_005422.4:c.1485A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-121125583-A-G
• chr11-121125583-A-C
• chr11-121125583-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005422.4(TECTA):​c.1485A>G​(p.Ala495Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,613,962 control chromosomes in the GnomAD database, including 407,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44421 hom., cov: 33)
  • Exomes 𝑓: 0.70 (363002 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -9.07
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-121125583-A-G is Benign according to our data. Variant chr11-121125583-A-G is described in ClinVar as Benign. ClinVar VariationId is 45315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 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.1485A>G	p.Ala495Ala	synonymous	Exon 8 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.2442A>G	p.Ala814Ala	synonymous	Exon 14 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.1485A>G	p.Ala495Ala	synonymous	Exon 8 of 24	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.1485A>G	p.Ala495Ala	synonymous	Exon 7 of 23	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.1485A>G	p.Ala495Ala	synonymous	Exon 8 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114975 AN: 152124 Hom.: 44364 Cov.: 33

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.744

GnomAD2 exomes AF: 0.703 AC: 176656 AN: 251170 AF XY: 0.704

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.674

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.697

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.703 AC: 1027389 AN: 1461720 Hom.: 363002 Cov.: 97 AF XY: 0.704 AC XY: 511674 AN XY: 727158

African (AFR) AF: 0.942 AC: 31525 AN: 33480

American (AMR) AF: 0.623 AC: 27852 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 16253 AN: 26136

East Asian (EAS) AF: 0.682 AC: 27060 AN: 39694

South Asian (SAS) AF: 0.721 AC: 62205 AN: 86258

European-Finnish (FIN) AF: 0.736 AC: 39230 AN: 53308

Middle Eastern (MID) AF: 0.704 AC: 4062 AN: 5768

European-Non Finnish (NFE) AF: 0.698 AC: 776418 AN: 1111964

Other (OTH) AF: 0.708 AC: 42784 AN: 60394

GnomAD4 genome AF: 0.756 AC: 115079 AN: 152242 Hom.: 44421 Cov.: 33 AF XY: 0.755 AC XY: 56178 AN XY: 74424

African (AFR) AF: 0.928 AC: 38577 AN: 41550

American (AMR) AF: 0.672 AC: 10275 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.674 AC: 3489 AN: 5174

South Asian (SAS) AF: 0.734 AC: 3536 AN: 4820

European-Finnish (FIN) AF: 0.724 AC: 7681 AN: 10608

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47056 AN: 68004

Other (OTH) AF: 0.742 AC: 1565 AN: 2110

Alfa AF: 0.707 Hom.: 25127

Bravo AF: 0.757

Asia WGS AF: 0.725 AC: 2522 AN: 3478

EpiCase AF: 0.689

EpiControl AF: 0.690

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Autosomal dominant nonsyndromic hearing loss 12 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 21 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.034
DANN	Benign	0.22
PhyloP100		-9.1
Mutation Taster		=83/17	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: rs536069; hg19: chr11-120996292; COSMIC: COSV50687976; COSMIC: COSV50687976;