10-112283790-C-G

Variant names:

• chr10-112283790-C-G
• NM_058222.3:c.56C>G

Variant summary

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

The NM_058222.3(TECTB):​c.56C>G​(p.Ser19Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TECTB NM_058222.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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.56C>G	p.Ser19Trp	missense_variant	Exon 2 of 11	ENST00000646139.2	NP_478129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTB	ENST00000646139.2	c.56C>G	p.Ser19Trp	missense_variant	Exon 2 of 11		NM_058222.3	ENSP00000494896.1
TECTB	ENST00000369422.4	c.56C>G	p.Ser19Trp	missense_variant	Exon 1 of 10	1		ENSP00000358430.3
TECTB	ENST00000643850.1	c.56C>G	p.Ser19Trp	missense_variant	Exon 2 of 11			ENSP00000495832.1
TECTB	ENST00000645243.1	c.56C>G	p.Ser19Trp	missense_variant	Exon 2 of 11			ENSP00000495514.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461616 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>G (p.S19W) alteration is located in exon 1 (coding exon 1) of the TECTB gene. This alteration results from a C to G substitution at nucleotide position 56, causing the serine (S) at amino acid position 19 to be replaced by a tryptophan (W). 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	Benign	0.22
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	.;T;.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D;.;D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.69	.;N;.;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.4	.;.;.;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	.;.;.;D
Sift4G	Uncertain	0.014	.;.;.;D
Polyphen		0.98	.;D;.;D
Vest4		0.53
MutPred		0.54		Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);
MVP		0.72
MPC		0.29
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.52

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: chr10-114043548;