chr11-121102587-A-C

Position:

• chr11-121102587-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005422.4(TECTA):​c.-1-78A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,047,042 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (270 hom., cov: 32)
  • Exomes 𝑓: 0.013 (248 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-121102587-A-C is Benign according to our data. Variant chr11-121102587-A-C is described in ClinVar as [Benign]. Clinvar id is 1244654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.-1-78A>C		intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.957-78A>C		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.-1-78A>C		intron_variant		5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000642222.1	c.-1-78A>C		intron_variant				ENSP00000493855	A1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5710 AN: 152142 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0310

GnomAD4 exome AF: 0.0131 AC: 11740 AN: 894782 Hom.: 248 AF XY: 0.0139 AC XY: 6498 AN XY: 468420

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.0296

Gnomad4 FIN exome AF: 0.000615

Gnomad4 NFE exome AF: 0.00865

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0376 AC: 5728 AN: 152260 Hom.: 270 Cov.: 32 AF XY: 0.0364 AC XY: 2713 AN XY: 74454

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00889

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0259 Hom.: 21

Bravo AF: 0.0427

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs56058285; hg19: chr11-120973296;