11-121105719-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005422.4(TECTA):c.65-112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,400,674 control chromosomes in the GnomAD database, including 177,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18643 hom., cov: 33)
  • Exomes 𝑓: 0.50 (159069 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.72

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-121105719-A-G is Benign according to our data. Variant chr11-121105719-A-G is described in ClinVar as [Benign]. Clinvar id is 1287175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECTA	NM_005422.4	c.65-112A>G		intron_variant		ENST00000392793.6
TBCEL-TECTA	NM_001378761.1	c.1022-112A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECTA	ENST00000392793.6	c.65-112A>G		intron_variant		5	NM_005422.4	P4
TECTA	ENST00000264037.2	c.65-112A>G		intron_variant		1		P4
TECTA	ENST00000642222.1	c.65-112A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74829 AN: 152048 Hom.: 18621 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.502 AC: 626692 AN: 1248506 Hom.: 159069 AF XY: 0.498 AC XY: 312023 AN XY: 626044

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.492 AC: 74902 AN: 152168 Hom.: 18643 Cov.: 33 AF XY: 0.485 AC XY: 36105 AN XY: 74390

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.500

Alfa AF: 0.512 Hom.: 33529

Bravo AF: 0.497

Asia WGS AF: 0.372 AC: 1298 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.031
Dann	Benign	0.30

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: rs504626; hg19: chr11-120976428; COSMIC: COSV50764203;