rs35107075

Variant names:

• chr11-121125534-C-G
• rs35107075
• NM_005422.4:c.1436C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-121125534-C-G
• chr11-121125534-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005422.4(TECTA):​c.1436C>G​(p.Pro479Arg) 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. 13/22 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. P479L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 8 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24010164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.1436C>G	p.Pro479Arg	missense_variant	Exon 8 of 24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.2393C>G	p.Pro798Arg	missense_variant	Exon 14 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.1436C>G	p.Pro479Arg	missense_variant	Exon 8 of 24	5	NM_005422.4	ENSP00000376543.1
TECTA	ENST00000264037.2	c.1436C>G	p.Pro479Arg	missense_variant	Exon 7 of 23	1		ENSP00000264037.2
TECTA	ENST00000642222.1	c.1436C>G	p.Pro479Arg	missense_variant	Exon 8 of 24			ENSP00000493855.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;.;L
PhyloP100		2.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.70	N;.;N
REVEL	Benign	0.079
Sift	Benign	0.12	T;.;T
Sift4G	Benign	0.28	T;.;T
Polyphen		0.91	P;.;P
Vest4		0.45
MutPred		0.47		Gain of catalytic residue at P479 (P = 0.066);Gain of catalytic residue at P479 (P = 0.066);Gain of catalytic residue at P479 (P = 0.066);
MVP		0.78
MPC		0.42
ClinPred		0.85	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.85
Mutation Taster		=82/18	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: rs35107075; hg19: chr11-120996243;