chr3-69763889-C-G

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

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.364
Variant links:
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 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
MITFNM_001354604.2 linkuse as main transcriptc.104+24188C>G intron_variant ENST00000352241.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MITFENST00000352241.9 linkuse as main transcriptc.104+24188C>G intron_variant 1 NM_001354604.2 P4O75030-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000504
AC:
1
AN:
198304
Hom.:
0
AF XY:
0.00000947
AC XY:
1
AN XY:
105574
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000119
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000163
AC:
2
AN:
1226830
Hom.:
0
Cov.:
31
AF XY:
0.00000166
AC XY:
1
AN XY:
602728
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000208
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0

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 submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaMay 09, 2019This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
7.6
DANN
Benign
0.97
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.39
T;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.082
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N
PROVEAN
Benign
-0.43
N;N
REVEL
Benign
0.030
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.065
T;T
Polyphen
0.0
.;B
Vest4
0.27
MutPred
0.31
Loss of methylation at K21 (P = 0.0839);Loss of methylation at K21 (P = 0.0839);
MVP
0.13
ClinPred
0.11
T
GERP RS
1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1441101806; hg19: chr3-69813040; API