10-112284525-C-G

Variant names:

• chr10-112284525-C-G
• rs143737351
• NM_058222.3:c.77-10C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058222.3(TECTB):​c.77-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TECTB NM_058222.3 intron
• Scores: Splicing: ADA: 0.001666
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 0 publications found

Genes affected

TECTB (HGNC:11721): (tectorin beta) This gene encodes a non-collagenous glycoprotein component of the tectorial membrane, which covers the auditory hair cells in the cochlea of the inner ear. A similar protein in mouse functions in low-frequency hearing. [provided by RefSeq, Jul 2013]

ENSG00000288938 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058222.3. 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
	TECTB	NM_058222.3	MANE Select	c.77-10C>G		intron	N/A	NP_478129.1	Q96PL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTB	ENST00000646139.2	MANE Select	c.77-10C>G		intron	N/A	ENSP00000494896.1	Q96PL2
	TECTB	ENST00000369422.4	TSL:1	c.77-10C>G		intron	N/A	ENSP00000358430.3	Q96PL2
	TECTB	ENST00000643850.1		c.77-10C>G		intron	N/A	ENSP00000495832.1	A0A2R8YGB5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442214 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715094

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 39248

South Asian (SAS) AF: 0.00 AC: 0 AN: 82482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1100758

Other (OTH) AF: 0.00 AC: 0 AN: 59588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.010		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: rs143737351; hg19: chr10-114044283;