NM_005422.4:c.2574C>G

Variant names:

• chr11-121129844-C-G
• NM_005422.4:c.2574C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_005422.4(TECTA):​c.2574C>G​(p.Asp858Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.2574C>G	p.Asp858Glu	missense_variant	Exon 10 of 24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.3531C>G	p.Asp1177Glu	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.2574C>G	p.Asp858Glu	missense_variant	Exon 10 of 24	5	NM_005422.4	ENSP00000376543.1
TECTA	ENST00000264037.2	c.2574C>G	p.Asp858Glu	missense_variant	Exon 9 of 23	1		ENSP00000264037.2
TECTA	ENST00000642222.1	c.2574C>G	p.Asp858Glu	missense_variant	Exon 10 of 24			ENSP00000493855.1
TECTA	ENST00000645008.1	c.-121C>G		upstream_gene_variant				ENSP00000496274.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

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: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.;D
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.73	.;T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D;.;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D;.;D
Sift4G	Pathogenic	0.0	D;.;D
Polyphen		1.0	D;.;D
Vest4		0.37
MutPred		0.79		Loss of catalytic residue at S857 (P = 0.3912);Loss of catalytic residue at S857 (P = 0.3912);Loss of catalytic residue at S857 (P = 0.3912);
MVP		0.75
MPC		1.0
ClinPred		0.95	D
GERP RS		-2.4
Varity_R		0.86
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-121000553;