chr11-121102355-A-C

Position:

• chr11-121102355-A-C

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.-1-310A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 152,282 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.024 (147 hom., cov: 32)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.246

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=-0.82).
• BP6: Variant 11-121102355-A-C is Benign according to our data. Variant chr11-121102355-A-C is described in ClinVar as [Benign]. Clinvar id is 1296878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.-1-310A>C		intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.957-310A>C		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.-1-310A>C		intron_variant		5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000642222.1	c.-1-310A>C		intron_variant				ENSP00000493855	A1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3668 AN: 152164 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0241 AC: 3673 AN: 152282 Hom.: 147 Cov.: 32 AF XY: 0.0229 AC XY: 1708 AN XY: 74462

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00436 Hom.: 4

Bravo AF: 0.0282

Asia WGS AF: 0.00664 AC: 24 AN: 3476

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

Dec 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.92
DANN	Benign	0.56

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: rs73599455; hg19: chr11-120973064;