rs727504781

chr11-121165264-TC-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_005422.4(TECTA):c.5273-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,591,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: TECTA NM_005422.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.07

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant 11-121165264-TC-T is Benign according to our data. Variant chr11-121165264-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 179309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECTA	NM_005422.4	c.5273-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000392793.6
TBCEL-TECTA	NM_001378761.1	c.6215-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECTA	ENST00000392793.6	c.5273-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_005422.4	P4

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000292 AC: 42 AN: 1438812 Hom.: 0 Cov.: 31 AF XY: 0.0000196 AC XY: 14 AN XY: 713102

Gnomad4 AFR exome AF: 0.00103

Gnomad4 AMR exome AF: 0.0000962

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000672

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74498

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000321

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 11, 2013

5273-8delC in Intron 15 of TECTA: This variant is not expected to have clinical significance because it is does not diverge from the splice site consensus seque nce and computational tools do not suggest an impact to splicing. In addition, t his variant has been identified in 0.2% (8/4264) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs727504781; hg19: chr11-121035973;