chr10-112286390-C-T

Variant names:

• chr10-112286390-C-T
• NM_058222.3:c.482C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_058222.3(TECTB):​c.482C>T​(p.Thr161Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TECTB NM_058222.3 missense, splice_region
• Scores: Splicing: ADA: 0.9920
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTB	NM_058222.3	c.482C>T	p.Thr161Ile	missense_variant, splice_region_variant	Exon 5 of 11	ENST00000646139.2	NP_478129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTB	ENST00000646139.2	c.482C>T	p.Thr161Ile	missense_variant, splice_region_variant	Exon 5 of 11		NM_058222.3	ENSP00000494896.1
TECTB	ENST00000369422.4	c.482C>T	p.Thr161Ile	missense_variant, splice_region_variant	Exon 4 of 10	1		ENSP00000358430.3
TECTB	ENST00000643850.1	c.512C>T	p.Thr171Ile	missense_variant, splice_region_variant	Exon 5 of 11			ENSP00000495832.1
TECTB	ENST00000645243.1	c.482C>T	p.Thr161Ile	missense_variant, splice_region_variant	Exon 5 of 11			ENSP00000495514.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482C>T (p.T161I) alteration is located in exon 4 (coding exon 4) of the TECTB gene. This alteration results from a C to T substitution at nucleotide position 482, causing the threonine (T) at amino acid position 161 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	.;D;.;D
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;.;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Uncertain	0.098	D
MutationAssessor	Benign	1.1	.;L;.;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	.;.;.;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.021	.;.;.;D
Sift4G	Uncertain	0.0070	.;.;.;D
Polyphen		0.92	.;P;.;P
Vest4		0.50
MutPred		0.49		.;Loss of phosphorylation at T161 (P = 0.1821);Loss of phosphorylation at T161 (P = 0.1821);Loss of phosphorylation at T161 (P = 0.1821);
MVP		0.87
MPC		0.27
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.30
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.89
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-114046148;