rs1796991

chr9-72702958-A-Cchr9-72702958-A-Gchr9-72702958-A-T

Variant summary

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

The NM_138691.3(TMC1):c.362+2315A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,720 control chromosomes in the GnomAD database, including 4,263 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 0.23 (4263 hom., cov: 30)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC1	NM_138691.3	c.362+2315A>C		intron_variant		ENST00000297784.10
TMC1	XM_017014256.2	c.365+2315A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC1	ENST00000297784.10	c.362+2315A>C		intron_variant		1	NM_138691.3	P2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34537 AN: 151602 Hom.: 4252 Cov.: 30

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.228 AC: 34571 AN: 151720 Hom.: 4263 Cov.: 30 AF XY: 0.233 AC XY: 17260 AN XY: 74120

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.222

Alfa AF: 0.136 Hom.: 317

Bravo AF: 0.230

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.40

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: rs1796991; hg19: chr9-75317874;