chr3-69763693-G-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001354604.2(MITF):c.104+23992G>T variant causes a intron change. The variant allele was found at a frequency of 0.00175 in 1,298,072 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0088 ( 21 hom., cov: 33)
Exomes 𝑓: 0.00081 ( 15 hom. )
Consequence
MITF
NM_001354604.2 intron
NM_001354604.2 intron
Scores
1
1
Splicing: ADA: 0.8492
2
Clinical Significance
Conservation
PhyloP100: 4.88
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 Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 3-69763693-G-T is Benign according to our data. Variant chr3-69763693-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 669675.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00882 (1343/152336) while in subpopulation AFR AF= 0.0312 (1299/41574). AF 95% confidence interval is 0.0298. There are 21 homozygotes in gnomad4. There are 657 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1341 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MITF | NM_001354604.2 | c.104+23992G>T | intron_variant | ENST00000352241.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.104+23992G>T | intron_variant | 1 | NM_001354604.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00881 AC: 1341AN: 152218Hom.: 22 Cov.: 33
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GnomAD4 exome AF: 0.000810 AC: 928AN: 1145736Hom.: 15 Cov.: 31 AF XY: 0.000772 AC XY: 428AN XY: 554440
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
Find out detailed SpliceAI scores and Pangolin per-transcript scores at