GeneBe

rs36038786

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138691.3(TMC1):​c.-195-13_-195-11delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TMC1
NM_138691.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Publications

0 publications found
Variant links:
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 Gene-Disease associations (from GenCC):
  • nonsyndromic genetic hearing loss
    Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics
  • autosomal recessive nonsyndromic hearing loss 7
    Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • autosomal dominant nonsyndromic hearing loss 36
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • autosomal dominant nonsyndromic hearing loss
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138691.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TMC1
NM_138691.3
MANE Select
c.-195-13_-195-11delTTT
intron
N/ANP_619636.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TMC1
ENST00000297784.10
TSL:1 MANE Select
c.-195-13_-195-11delTTT
intron
N/AENSP00000297784.6Q8TDI8
TMC1
ENST00000340019.4
TSL:5
c.-195-13_-195-11delTTT
intron
N/AENSP00000341433.3Q8TDI8
TMC1
ENST00000645208.2
c.-195-13_-195-11delTTT
intron
N/AENSP00000494684.1Q8TDI8

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
194742
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
111670
African (AFR)
AF:
0.00
AC:
0
AN:
4518
American (AMR)
AF:
0.00
AC:
0
AN:
10360
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
5678
East Asian (EAS)
AF:
0.00
AC:
0
AN:
7348
South Asian (SAS)
AF:
0.00
AC:
0
AN:
40204
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
8220
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1574
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
107732
Other (OTH)
AF:
0.00
AC:
0
AN:
9108
GnomAD4 genome
Cov.:
24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs36038786; hg19: chr9-75242814; API