3-69959291-G-C
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001354604.2(MITF):c.1050G>C(p.Lys350Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K350E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001354604.2 missense
Scores
Clinical Significance
Conservation
Publications
- Tietz syndromeInheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics
- Waardenburg syndrome type 2Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Waardenburg syndrome type 2AInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
- melanoma, cutaneous malignant, susceptibility to, 8Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafnessInheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
- renal cell carcinomaInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- Waardenburg syndromeInheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
- Waardenburg-Shah syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MITF | ENST00000352241.9 | c.1050G>C | p.Lys350Asn | missense_variant | Exon 9 of 10 | 1 | NM_001354604.2 | ENSP00000295600.8 | ||
MITF | ENST00000394351.9 | c.729G>C | p.Lys243Asn | missense_variant | Exon 8 of 9 | 1 | NM_000248.4 | ENSP00000377880.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
MITF-related disorder Uncertain:1
The MITF c.729G>C variant is predicted to result in the amino acid substitution p.Lys243Asn. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at