chr10-112286198-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ENSG00000288938 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058222.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTB	NM_058222.3	MANE Select	c.395C>T	p.Ala132Val	missense	Exon 4 of 11	NP_478129.1	Q96PL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTB	ENST00000646139.2	MANE Select	c.395C>T	p.Ala132Val	missense	Exon 4 of 11	ENSP00000494896.1	Q96PL2
	TECTB	ENST00000369422.4	TSL:1	c.395C>T	p.Ala132Val	missense	Exon 3 of 10	ENSP00000358430.3	Q96PL2
	TECTB	ENST00000643850.1		c.395C>T	p.Ala132Val	missense	Exon 4 of 11	ENSP00000495832.1	A0A2R8YGB5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.025	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.7
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
Vest4		0.49
MutPred		0.65		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
Mutation Taster		=44/56	disease causing

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

Other links and lift over

hg19: chr10-114045956;