rs504626

Variant names:

• chr11-121105719-A-G
• rs504626
• NM_005422.4:c.65-112A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378761.1(TBCEL-TECTA):​c.1022-112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,400,674 control chromosomes in the GnomAD database, including 177,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18643 hom., cov: 33)
  • Exomes 𝑓: 0.50 (159069 hom.)
• Consequence: TBCEL-TECTA NM_001378761.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.72
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-121105719-A-G is Benign according to our data. Variant chr11-121105719-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378761.1. 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.65-112A>G		intron	N/A	NP_005413.2
	TBCEL-TECTA	NM_001378761.1		c.1022-112A>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.65-112A>G		intron	N/A	ENSP00000376543.1
	TECTA	ENST00000264037.2	TSL:1	c.65-112A>G		intron	N/A	ENSP00000264037.2
	TBCEL-TECTA	ENST00000645041.1		c.974-112A>G		intron	N/A	ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74829 AN: 152048 Hom.: 18621 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.502 AC: 626692 AN: 1248506 Hom.: 159069 AF XY: 0.498 AC XY: 312023 AN XY: 626044

African (AFR) AF: 0.518 AC: 15155 AN: 29248

American (AMR) AF: 0.375 AC: 13945 AN: 37168

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 14597 AN: 24420

East Asian (EAS) AF: 0.375 AC: 13662 AN: 36452

South Asian (SAS) AF: 0.407 AC: 31654 AN: 77812

European-Finnish (FIN) AF: 0.440 AC: 18257 AN: 41518

Middle Eastern (MID) AF: 0.512 AC: 2073 AN: 4050

European-Non Finnish (NFE) AF: 0.519 AC: 490486 AN: 944434

Other (OTH) AF: 0.503 AC: 26863 AN: 53404

GnomAD4 genome AF: 0.492 AC: 74902 AN: 152168 Hom.: 18643 Cov.: 33 AF XY: 0.485 AC XY: 36105 AN XY: 74390

African (AFR) AF: 0.509 AC: 21143 AN: 41518

American (AMR) AF: 0.441 AC: 6742 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2035 AN: 5178

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4820

European-Finnish (FIN) AF: 0.434 AC: 4588 AN: 10582

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34712 AN: 67990

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.508 Hom.: 76230

Bravo AF: 0.497

Asia WGS AF: 0.372 AC: 1298 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.031
DANN	Benign	0.30
PhyloP100		-2.7
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: rs504626; hg19: chr11-120976428; COSMIC: COSV50764203;