rs520805

Positions:

• chr11-121130065-T-A
• chr11-121130065-T-C
• chr11-121130065-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005422.4(TECTA):​c.2795T>A​(p.Val932Asp) 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 pathogenic 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. V932A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

Genes affected

TECTA (HGNC:11720): (tectorin alpha) The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]

TBCEL-TECTA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.2795T>A	p.Val932Asp	missense_variant	10/24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.3752T>A	p.Val1251Asp	missense_variant	16/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.2795T>A	p.Val932Asp	missense_variant	10/24	5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000264037.2	c.2795T>A	p.Val932Asp	missense_variant	9/23	1		ENSP00000264037	P4
TECTA	ENST00000642222.1	c.2795T>A	p.Val932Asp	missense_variant	10/24			ENSP00000493855	A1
TECTA	ENST00000645008.1	c.104T>A	p.Val35Asp	missense_variant	1/15			ENSP00000496274

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Uncertain	0.038	D
MutationAssessor	Uncertain	2.0	M;.;M
MutationTaster	Benign	0.0000069	P;P
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.080	N;.;N
REVEL	Uncertain	0.56
Sift	Benign	0.066	T;.;T
Sift4G	Benign	0.072	T;.;T
Polyphen		0.81	P;.;P
Vest4		0.80
MutPred		0.62		Loss of stability (P = 0.0897);Loss of stability (P = 0.0897);Loss of stability (P = 0.0897);
MVP		0.83
MPC		0.79
ClinPred		0.73	D
GERP RS		4.7
Varity_R		0.38
gMVP		0.90

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

LitVar

Other links and lift over

dbSNP: rs520805; hg19: chr11-121000774;