chr3-69763889-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001354604.2(MITF):c.104+24188C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,379,070 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
MITF
NM_001354604.2 intron
NM_001354604.2 intron
Scores
1
15
Clinical Significance
Conservation
PhyloP100: 0.364
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=0.0818426).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MITF | NM_001354604.2 | c.104+24188C>G | intron_variant | ENST00000352241.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.104+24188C>G | intron_variant | 1 | NM_001354604.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000504 AC: 1AN: 198304Hom.: 0 AF XY: 0.00000947 AC XY: 1AN XY: 105574
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GnomAD4 exome AF: 0.00000163 AC: 2AN: 1226830Hom.: 0 Cov.: 31 AF XY: 0.00000166 AC XY: 1AN XY: 602728
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Tietz syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | May 09, 2019 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BP4. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
0.0
.;B
Vest4
0.27
MutPred
Loss of methylation at K21 (P = 0.0839);Loss of methylation at K21 (P = 0.0839);
MVP
ClinPred
T
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at