rs12275038

Variant names:

• chr11-121146109-G-A
• rs12275038
• NM_005422.4:c.4098G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-121146109-G-A
• chr11-121146109-G-C
• chr11-121146109-G-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.4098G>A​(p.Thr1366Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,607,516 control chromosomes in the GnomAD database, including 41,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (7227 hom., cov: 33)
  • Exomes 𝑓: 0.21 (34607 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -4.01
• Publications: 11 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=-0.77).
• BP6: Variant 11-121146109-G-A is Benign according to our data. Variant chr11-121146109-G-A is described in ClinVar as Benign. ClinVar VariationId is 45329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 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.4098G>A	p.Thr1366Thr	synonymous	Exon 12 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.5055G>A	p.Thr1685Thr	synonymous	Exon 18 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.4098G>A	p.Thr1366Thr	synonymous	Exon 12 of 24	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.4098G>A	p.Thr1366Thr	synonymous	Exon 11 of 23	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.4098G>A	p.Thr1366Thr	synonymous	Exon 12 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41570 AN: 152094 Hom.: 7215 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.188 AC: 44846 AN: 238882 AF XY: 0.185

Gnomad AFR exome AF: 0.506

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.00248

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.207 AC: 301908 AN: 1455304 Hom.: 34607 Cov.: 33 AF XY: 0.205 AC XY: 148106 AN XY: 724178

African (AFR) AF: 0.506 AC: 16940 AN: 33472

American (AMR) AF: 0.117 AC: 5234 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4086 AN: 26136

East Asian (EAS) AF: 0.00139 AC: 55 AN: 39700

South Asian (SAS) AF: 0.137 AC: 11795 AN: 86246

European-Finnish (FIN) AF: 0.223 AC: 10514 AN: 47220

Middle Eastern (MID) AF: 0.180 AC: 1018 AN: 5670

European-Non Finnish (NFE) AF: 0.216 AC: 239879 AN: 1111812

Other (OTH) AF: 0.205 AC: 12387 AN: 60324

GnomAD4 genome AF: 0.273 AC: 41616 AN: 152212 Hom.: 7227 Cov.: 33 AF XY: 0.266 AC XY: 19830 AN XY: 74416

African (AFR) AF: 0.489 AC: 20307 AN: 41516

American (AMR) AF: 0.171 AC: 2609 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.00443 AC: 23 AN: 5190

South Asian (SAS) AF: 0.146 AC: 707 AN: 4832

European-Finnish (FIN) AF: 0.215 AC: 2280 AN: 10588

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14360 AN: 68010

Other (OTH) AF: 0.263 AC: 555 AN: 2110

Alfa AF: 0.225 Hom.: 6735

Bravo AF: 0.280

Asia WGS AF: 0.0920 AC: 322 AN: 3478

EpiCase AF: 0.208

EpiControl AF: 0.210

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 12 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 21 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.069
DANN	Benign	0.48
PhyloP100		-4.0
Mutation Taster		=86/14	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: rs12275038; hg19: chr11-121016818;