NM_138691.3:c.-195-12_-195-11delTT

Variant names:

• chr9-72627898-ATT-A
• rs36038786
• NM_138691.3:c.-195-12_-195-11delTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_138691.3(TMC1):​c.-195-12_-195-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 342,442 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00217 (421/193602) while in subpopulation AMR AF= 0.00448 (46/10258). AF 95% confidence interval is 0.00345. There are 0 homozygotes in gnomad4_exome. There are 262 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC1	NM_138691.3	c.-195-12_-195-11delTT		intron_variant	Intron 3 of 23	ENST00000297784.10	NP_619636.2
TMC1	XM_017014256.2	c.19+11432_19+11433delTT		intron_variant	Intron 2 of 20		XP_016869745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC1	ENST00000297784.10	c.-195-22_-195-21delTT		intron_variant	Intron 3 of 23	1	NM_138691.3	ENSP00000297784.6

Frequencies

GnomAD3 genomes AF: 0.000303 AC: 45 AN: 148758 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00201

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000782

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.000205

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000597

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00217 AC: 421 AN: 193602 Hom.: 0 AF XY: 0.00236 AC XY: 262 AN XY: 110974

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00448

Gnomad4 ASJ exome AF: 0.00177

Gnomad4 EAS exome AF: 0.00413

Gnomad4 SAS exome AF: 0.00309

Gnomad4 FIN exome AF: 0.00318

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.000302 AC: 45 AN: 148840 Hom.: 0 Cov.: 24 AF XY: 0.000386 AC XY: 28 AN XY: 72538

Gnomad4 AFR AF: 0.0000738

Gnomad4 AMR AF: 0.00201

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000785

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.000205

Gnomad4 NFE AF: 0.0000597

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs36038786; hg19: chr9-75242814;