3-69879358-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001354604.2(MITF):c.329C>T(p.Thr110Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T110T) has been classified as Benign.
Frequency
Consequence
NM_001354604.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MITF | NM_001354604.2 | c.329C>T | p.Thr110Met | missense_variant | 2/10 | ENST00000352241.9 | NP_001341533.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.329C>T | p.Thr110Met | missense_variant | 2/10 | 1 | NM_001354604.2 | ENSP00000295600.8 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000165 AC: 41AN: 248876Hom.: 0 AF XY: 0.000178 AC XY: 24AN XY: 135056
GnomAD4 exome AF: 0.000139 AC: 203AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.000158 AC XY: 115AN XY: 727244
GnomAD4 genome AF: 0.000184 AC: 28AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74494
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 16, 2015 | The p.Thr110Met variant in MITF has not been previously reported in individuals with hearing loss, but has been identified in 15/66632 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1 90215588). Although this variant has been seen in the general population, its fr equency is not high enough to rule out a pathogenic role. Computational predicti on tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Thr110Met variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
MITF-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 27, 2023 | The MITF c.329C>T variant is predicted to result in the amino acid substitution p.Thr110Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of European (Non-Finnish) descent in gnomAD. It is interpreted in ClinVar as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/228855). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at