9-72671401-A-T

Position:

• chr9-72671401-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_138691.3(TMC1):​c.17-17308A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,114 control chromosomes in the GnomAD database, including 4,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.24 (4762 hom., cov: 32)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

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]

TMC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-72671401-A-T is Benign according to our data. Variant chr9-72671401-A-T is described in Lovd as [Benign].
• 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	Protein	UniProt
TMC1	NM_138691.3	c.17-17308A>T		intron_variant		ENST00000297784.10	NP_619636.2
TMC1	XM_017014256.2	c.20-17308A>T		intron_variant			XP_016869745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC1	ENST00000297784.10	c.17-17308A>T		intron_variant		1	NM_138691.3	ENSP00000297784.6

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36625 AN: 151996 Hom.: 4749 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.241 AC: 36663 AN: 152114 Hom.: 4762 Cov.: 32 AF XY: 0.245 AC XY: 18226 AN XY: 74342

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.234

Alfa AF: 0.118 Hom.: 191

Bravo AF: 0.245

Asia WGS AF: 0.351 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.79

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: rs1417619; hg19: chr9-75286317;