chr11-121130010-A-T

Variant names:

• chr11-121130010-A-T
• rs1303790601
• NM_005422.4:c.2740A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005422.4(TECTA):​c.2740A>T​(p.Ile914Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3263929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.2740A>T	p.Ile914Phe	missense_variant	Exon 10 of 24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.3697A>T	p.Ile1233Phe	missense_variant	Exon 16 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.2740A>T	p.Ile914Phe	missense_variant	Exon 10 of 24	5	NM_005422.4	ENSP00000376543.1
TECTA	ENST00000264037.2	c.2740A>T	p.Ile914Phe	missense_variant	Exon 9 of 23	1		ENSP00000264037.2
TECTA	ENST00000642222.1	c.2740A>T	p.Ile914Phe	missense_variant	Exon 10 of 24			ENSP00000493855.1
TECTA	ENST00000645008.1	c.46A>T	p.Ile16Phe	missense_variant	Exon 1 of 15			ENSP00000496274.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74358

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.36	T;.;T
Eigen	Benign	-0.066
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.0	M;.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.4	N;.;N
REVEL	Uncertain	0.45
Sift	Benign	0.13	T;.;T
Sift4G	Benign	0.26	T;.;T
Polyphen		0.49	P;.;P
Vest4		0.42
MutPred		0.59		Gain of catalytic residue at I914 (P = 0.1559);Gain of catalytic residue at I914 (P = 0.1559);Gain of catalytic residue at I914 (P = 0.1559);
MVP		0.80
MPC		0.60
ClinPred		0.41	T
GERP RS		0.70
Varity_R		0.20
gMVP		0.75

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: rs1303790601; hg19: chr11-121000719;