chr3-69866343-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001354604.2(MITF):c.105-12791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,613,700 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
MITF
NM_001354604.2 intron
NM_001354604.2 intron
Scores
15
Clinical Significance
Conservation
PhyloP100: 0.830
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.046447217).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000125 (19/152194) while in subpopulation NFE AF= 0.000191 (13/68032). AF 95% confidence interval is 0.000112. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MITF | NM_001354604.2 | c.105-12791A>G | intron_variant | ENST00000352241.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.105-12791A>G | intron_variant | 1 | NM_001354604.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152194Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
19
AN:
152194
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000104 AC: 26AN: 248948Hom.: 0 AF XY: 0.0000963 AC XY: 13AN XY: 135060
GnomAD3 exomes
AF:
AC:
26
AN:
248948
Hom.:
AF XY:
AC XY:
13
AN XY:
135060
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000224 AC: 327AN: 1461506Hom.: 0 Cov.: 31 AF XY: 0.000227 AC XY: 165AN XY: 727010
GnomAD4 exome
AF:
AC:
327
AN:
1461506
Hom.:
Cov.:
31
AF XY:
AC XY:
165
AN XY:
727010
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74356
GnomAD4 genome
?
AF:
AC:
19
AN:
152194
Hom.:
Cov.:
32
AF XY:
AC XY:
9
AN XY:
74356
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
12
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MITF-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 30, 2023 | The MITF c.53A>G variant is predicted to result in the amino acid substitution p.Tyr18Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-69915494-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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
D;D;D;D;N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
ClinPred
T
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at