rs1630623

Positions:

• chr9-72725323-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138691.3(TMC1):​c.363-14796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.30 (4394 hom., cov: 18)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC1	NM_138691.3	c.363-14796A>G		intron_variant		ENST00000297784.10
TMC1	XM_017014256.2	c.366-14796A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC1	ENST00000297784.10	c.363-14796A>G		intron_variant		1	NM_138691.3	P2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 31388 AN: 106252 Hom.: 4390 Cov.: 18

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.295 AC: 31391 AN: 106232 Hom.: 4394 Cov.: 18 AF XY: 0.307 AC XY: 15344 AN XY: 49986

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.295

Alfa AF: 0.214 Hom.: 399

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs1630623; hg19: chr9-75340239;