10-112298073-C-T

Variant names:

• chr10-112298073-C-T
• rs767180634
• NM_058222.3:c.676C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_058222.3(TECTB):​c.676C>T​(p.Pro226Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P226T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TECTB NM_058222.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27484566).

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.676C>T	p.Pro226Ser	missense	Exon 8 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.676C>T	p.Pro226Ser	missense	Exon 8 of 11	ENSP00000494896.1	Q96PL2
	TECTB	ENST00000369422.4	TSL:1	c.676C>T	p.Pro226Ser	missense	Exon 7 of 10	ENSP00000358430.3	Q96PL2
	TECTB	ENST00000643850.1		c.706C>T	p.Pro236Ser	missense	Exon 8 of 11	ENSP00000495832.1	A0A2R8YGB5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.51
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-0.20
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.79	N
PhyloP100		2.2
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.23
Sift	Benign	0.43	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.48		Loss of methylation at K223 (P = 0.0894)
MVP		0.71
MPC		0.042
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.19
gMVP		0.45
Mutation Taster		=89/11	polymorphism

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

dbSNP: rs767180634; hg19: chr10-114057831;