rs597345

Variant names:

• chr11-121117415-A-G
• rs597345
• NM_005422.4:c.791-891A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005422.4(TECTA):​c.791-891A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,126 control chromosomes in the GnomAD database, including 13,242 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13242 hom., cov: 33)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005422.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.791-891A>G		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.1748-891A>G		intron	N/A	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.791-891A>G		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.791-891A>G		intron	N/A	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.791-891A>G		intron	N/A	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59703 AN: 152008 Hom.: 13234 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59732 AN: 152126 Hom.: 13242 Cov.: 33 AF XY: 0.389 AC XY: 28955 AN XY: 74362

African (AFR) AF: 0.172 AC: 7161 AN: 41526

American (AMR) AF: 0.443 AC: 6783 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1847 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1690 AN: 5176

South Asian (SAS) AF: 0.334 AC: 1607 AN: 4816

European-Finnish (FIN) AF: 0.489 AC: 5170 AN: 10562

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34037 AN: 67968

Other (OTH) AF: 0.408 AC: 861 AN: 2110

Alfa AF: 0.432 Hom.: 2376

Bravo AF: 0.383

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.55
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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: rs597345; hg19: chr11-120988124;