rs2069390
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001384361.1(PMEL):c.76+75T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,569,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000063 ( 0 hom. )
Consequence
PMEL
NM_001384361.1 intron
NM_001384361.1 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.29
Genes affected
PMEL (HGNC:10880): (premelanosome protein) This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMEL | NM_001384361.1 | c.76+75T>A | intron_variant | ENST00000548747.6 | NP_001371290.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548747.6 | c.76+75T>A | intron_variant | 1 | NM_001384361.1 | ENSP00000448828.1 |
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152216Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000635 AC: 9AN: 1417746Hom.: 0 AF XY: 0.00000706 AC XY: 5AN XY: 707852
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74360
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ClinVar
Not reported inComputational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at