9-72627898-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138691.3(TMC1):c.-195-11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 330,280 control chromosomes in the GnomAD database, including 7,012 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4217 hom., cov: 24)
  • Exomes 𝑓: 0.30 (2795 hom.)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420

Genes affected

TMC1 (HGNC:16513): (transmembrane channel like 1) This gene is considered a member of a gene family predicted to encode transmembrane proteins. The specific function of this gene is unknown; however, it is known to be required for normal function of cochlear hair cells. Mutations in this gene have been associated with progressive postlingual hearing loss and profound prelingual deafness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-72627898-AT-A is Benign according to our data. Variant chr9-72627898-AT-A is described in ClinVar as [Benign]. Clinvar id is 1300604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC1	NM_138691.3	c.-195-11del		intron_variant		ENST00000297784.10
TMC1	XM_017014256.2	c.19+11433del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC1	ENST00000297784.10	c.-195-11del		intron_variant		1	NM_138691.3	P2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 34715 AN: 148546 Hom.: 4207 Cov.: 24

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.299 AC: 54387 AN: 181652 Hom.: 2795 Cov.: 0 AF XY: 0.305 AC XY: 31885 AN XY: 104452

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.234 AC: 34750 AN: 148628 Hom.: 4217 Cov.: 24 AF XY: 0.238 AC XY: 17261 AN XY: 72416

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.231

Bravo AF: 0.232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs36038786; hg19: chr9-75242814;