rs516678

Variant names:

• chr11-121168200-T-G
• rs516678
• NM_005422.4:c.5733T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-121168200-T-G
• chr11-121168200-T-C

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.5733T>G​(p.Val1911Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,614,236 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (203 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (184 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -8.59
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-121168200-T-G is Benign according to our data. Variant chr11-121168200-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 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.5733T>G	p.Val1911Val	synonymous	Exon 19 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.6675T>G	p.Val2225Val	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.5733T>G	p.Val1911Val	synonymous	Exon 19 of 24	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.5733T>G	p.Val1911Val	synonymous	Exon 18 of 23	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.5718T>G	p.Val1906Val	synonymous	Exon 19 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4533 AN: 152236 Hom.: 205 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.0224

GnomAD2 exomes AF: 0.00791 AC: 1989 AN: 251472 AF XY: 0.00581

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00650

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00317 AC: 4629 AN: 1461882 Hom.: 184 Cov.: 32 AF XY: 0.00276 AC XY: 2004 AN XY: 727244

African (AFR) AF: 0.105 AC: 3504 AN: 33478

American (AMR) AF: 0.00733 AC: 328 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5768

European-Non Finnish (NFE) AF: 0.000261 AC: 290 AN: 1112002

Other (OTH) AF: 0.00730 AC: 441 AN: 60396

GnomAD4 genome AF: 0.0298 AC: 4542 AN: 152354 Hom.: 203 Cov.: 33 AF XY: 0.0290 AC XY: 2159 AN XY: 74502

African (AFR) AF: 0.101 AC: 4214 AN: 41578

American (AMR) AF: 0.0156 AC: 239 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68032

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.0136 Hom.: 58

Bravo AF: 0.0345

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (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	-0.87
CADD	Benign	0.031
DANN	Benign	0.56
PhyloP100		-8.6
Mutation Taster		=78/22	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: rs516678; hg19: chr11-121038909;