Genetic Variant TECTB:c.77-10C>T (chr10-112284525-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_058222.3(TECTB):c.77-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,594,504 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 3 hom. )

Consequence

TECTB
NM_058222.3 intron

Scores

Splicing: ADA: 0.000008836

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.458

Variant links:

Genes affected

TECTB (HGNC:11721): (tectorin beta) This gene encodes a non-collagenous glycoprotein component of the tectorial membrane, which covers the auditory hair cells in the cochlea of the inner ear. A similar protein in mouse functions in low-frequency hearing. [provided by RefSeq, Jul 2013]

TECTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 10-112284525-C-T is Benign according to our data. Variant chr10-112284525-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3053331.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTB	NM_058222.3 link	c.77-10C>T		intron_variant	Intron 2 of 10	ENST00000646139.2	NP_478129.1	Q96PL2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TECTB	ENST00000646139.2 link	c.77-10C>T	intron_variant	Intron 2 of 10		NM_058222.3	ENSP00000494896.1	Q96PL2
TECTB	ENST00000369422.4 link	c.77-10C>T	intron_variant	Intron 1 of 9	1		ENSP00000358430.3	Q96PL2
TECTB	ENST00000643850.1 link	c.77-10C>T	intron_variant	Intron 2 of 10			ENSP00000495832.1	A0A2R8YGB5
TECTB	ENST00000645243.1 link	c.77-10C>T	intron_variant	Intron 2 of 10			ENSP00000495514.1	A0A2R8Y6R9

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

421

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00898

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

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:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000862

AC:

207

AN:

240098

Hom.:

AF XY:

0.000680

AC XY:

AN XY:

129344

show subpopulations

Gnomad AFR exome

AF:

0.00935

Gnomad AMR exome

AF:

0.000948

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000183

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000331

AC:

477

AN:

1442210

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

214

AN XY:

715092

show subpopulations

Gnomad4 AFR exome

AF:

0.00867

Gnomad4 AMR exome

AF:

0.00125

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:

0.0000927

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.00276

AC:

421

AN:

152294

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00895

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00309

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TECTB-related disorder

Benign:1

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.63

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000088

dbscSNV1_RF

Benign

0.038

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over