rs779387274
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001354604.2(MITF):c.105-12836C>T variant causes a intron change. The variant allele was found at a frequency of 0.0000192 in 1,461,442 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 Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
MITF
NM_001354604.2 intron
NM_001354604.2 intron
Scores
1
3
11
Clinical Significance
Conservation
PhyloP100: 5.67
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15411964).
BP6
?
Variant 3-69866298-C-T is Benign according to our data. Variant chr3-69866298-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227547.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome4 at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MITF | NM_001354604.2 | c.105-12836C>T | intron_variant | ENST00000352241.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.105-12836C>T | intron_variant | 1 | NM_001354604.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 248930Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135070
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461442Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726984
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
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?
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2
Asia WGS
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1
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3478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 29, 2015 | p.Ala3Val in exon 01c of MITF: This variant is not expected to have clinical si gnificance because the alanine (Ala) residue at position 3 is not conserved thro ugh species, with Egyptian jerboa, elephant and Cape elephant shrew all having a valine (Val) at this position. Additional computational analyses suggest that this variant may not impact the protein. It has been identified in 1/66732 Eur opean chromosomes and 1/16512 South Asian chromosomes by the Exome Aggregation C onsortium (ExAC, http://exac.broadinstitute.org). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Uncertain
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
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MVP
ClinPred
T
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at