10-112284696-A-C

Position:

• chr10-112284696-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_058222.3(TECTB):​c.238A>C​(p.Asn80His) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 8.93

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 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity TECTB_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECTB	NM_058222.3	c.238A>C	p.Asn80His	missense_variant	3/11	ENST00000646139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECTB	ENST00000646139.2	c.238A>C	p.Asn80His	missense_variant	3/11		NM_058222.3	P1
TECTB	ENST00000369422.4	c.238A>C	p.Asn80His	missense_variant	2/10	1		P1
TECTB	ENST00000643850.1	c.238A>C	p.Asn80His	missense_variant	3/11
TECTB	ENST00000645243.1	c.238A>C	p.Asn80His	missense_variant	3/11

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.238A>C (p.N80H) alteration is located in exon 2 (coding exon 2) of the TECTB gene. This alteration results from a A to C substitution at nucleotide position 238, causing the asparagine (N) at amino acid position 80 to be replaced by a histidine (H). 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	0.55
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
Polyphen		1.0	.;D;.;D
Vest4		0.87
MutPred		0.47		Gain of ubiquitination at K79 (P = 0.0719);Gain of ubiquitination at K79 (P = 0.0719);Gain of ubiquitination at K79 (P = 0.0719);Gain of ubiquitination at K79 (P = 0.0719);
MVP		0.85
MPC		0.29
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.71

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: chr10-114044454;