chr10-112286198-C-T

Variant names:

• chr10-112286198-C-T
• NM_058222.3:c.395C>T

Variant summary

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

The NM_058222.3(TECTB):​c.395C>T​(p.Ala132Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TECTB NM_058222.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

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.395C>T	p.Ala132Val	missense_variant	Exon 4 of 11	ENST00000646139.2	NP_478129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTB	ENST00000646139.2	c.395C>T	p.Ala132Val	missense_variant	Exon 4 of 11		NM_058222.3	ENSP00000494896.1
TECTB	ENST00000369422.4	c.395C>T	p.Ala132Val	missense_variant	Exon 3 of 10	1		ENSP00000358430.3
TECTB	ENST00000643850.1	c.395C>T	p.Ala132Val	missense_variant	Exon 4 of 11			ENSP00000495832.1
TECTB	ENST00000645243.1	c.395C>T	p.Ala132Val	missense_variant	Exon 4 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

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.395C>T (p.A132V) alteration is located in exon 3 (coding exon 3) of the TECTB gene. This alteration results from a C to T substitution at nucleotide position 395, causing the alanine (A) at amino acid position 132 to be replaced by a valine (V). 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	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	.;T;.;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;.;D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Uncertain	-0.025	T
MutationAssessor	Benign	1.4	.;L;.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.74	.;.;.;N
REVEL	Uncertain	0.41
Sift	Benign	0.19	.;.;.;T
Sift4G	Uncertain	0.013	.;.;.;D
Polyphen		0.97	.;D;.;D
Vest4		0.49
MutPred		0.65		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.71
MPC		0.28
ClinPred		0.90	D
GERP RS		6.2
Varity_R		0.19
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-114045956;