11-121168101-C-T

Variant names:

• chr11-121168101-C-T
• rs2155369
• NM_005422.4:c.5634C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005422.4(TECTA):​c.5634C>T​(p.Ser1878Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,960 control chromosomes in the GnomAD database, including 19,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1559 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17589 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.0610
• Publications: 26 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-121168101-C-T is Benign according to our data. Variant chr11-121168101-C-T is described in ClinVar as Benign. ClinVar VariationId is 45338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.061 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 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.5634C>T	p.Ser1878Ser	synonymous	Exon 19 of 24	NP_005413.2
	TBCEL-TECTA	NM_001378761.1		c.6576C>T	p.Ser2192Ser	synonymous	Exon 25 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.5634C>T	p.Ser1878Ser	synonymous	Exon 19 of 24	ENSP00000376543.1
	TECTA	ENST00000264037.2	TSL:1	c.5634C>T	p.Ser1878Ser	synonymous	Exon 18 of 23	ENSP00000264037.2
	TECTA	ENST00000642222.1		c.5619C>T	p.Ser1873Ser	synonymous	Exon 19 of 24	ENSP00000493855.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18215 AN: 152068 Hom.: 1556 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.170 AC: 42809 AN: 251466 AF XY: 0.176

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.298

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.141 AC: 206629 AN: 1461774 Hom.: 17589 Cov.: 33 AF XY: 0.148 AC XY: 107673 AN XY: 727188

African (AFR) AF: 0.0253 AC: 848 AN: 33480

American (AMR) AF: 0.202 AC: 9015 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4135 AN: 26134

East Asian (EAS) AF: 0.290 AC: 11524 AN: 39698

South Asian (SAS) AF: 0.313 AC: 27001 AN: 86254

European-Finnish (FIN) AF: 0.113 AC: 6060 AN: 53418

Middle Eastern (MID) AF: 0.234 AC: 1351 AN: 5768

European-Non Finnish (NFE) AF: 0.123 AC: 136955 AN: 1111914

Other (OTH) AF: 0.161 AC: 9740 AN: 60388

GnomAD4 genome AF: 0.120 AC: 18223 AN: 152186 Hom.: 1559 Cov.: 32 AF XY: 0.125 AC XY: 9330 AN XY: 74424

African (AFR) AF: 0.0335 AC: 1391 AN: 41526

American (AMR) AF: 0.185 AC: 2830 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1593 AN: 5182

South Asian (SAS) AF: 0.329 AC: 1587 AN: 4818

European-Finnish (FIN) AF: 0.107 AC: 1136 AN: 10604

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8583 AN: 67994

Other (OTH) AF: 0.155 AC: 329 AN: 2116

Alfa AF: 0.136 Hom.: 3609

Bravo AF: 0.117

Asia WGS AF: 0.279 AC: 972 AN: 3478

EpiCase AF: 0.144

EpiControl AF: 0.139

ClinVar

ClinVar submissions as Germline

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	-0.29
CADD	Benign	8.5
DANN	Benign	0.69
PhyloP100		-0.061
Mutation Taster		=99/1	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: rs2155369; hg19: chr11-121038810; COSMIC: COSV50715554;