chr3-69866345-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001354604.2(MITF):c.105-12789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,366 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MITF
NM_001354604.2 intron
NM_001354604.2 intron
Scores
3
13
Splicing: ADA: 0.7931
2
Clinical Significance
Conservation
PhyloP100: 2.60
Genes affected
MITF (HGNC:7105): (melanocyte inducing transcription factor) The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13689339).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MITF | NM_001354604.2 | c.105-12789C>T | intron_variant | ENST00000352241.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.105-12789C>T | intron_variant | 1 | NM_001354604.2 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461366Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726946
GnomAD4 exome
AF:
AC:
1
AN:
1461366
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
726946
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 18, 2016 | The p.Leu19Phe variant in MITF has not been previously reported in individuals w ith hearing loss or Waardenburg syndrome and was absent from large population st udies. Computational prediction tools and conservation analysis suggest that thi s variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p .Leu19Phe variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of glycosylation at Y18 (P = 0.0054);Gain of glycosylation at Y18 (P = 0.0054);
MVP
ClinPred
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
Find out detailed SpliceAI scores and Pangolin per-transcript scores at