rs2069391
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1
The NM_006928.5(PMEL):c.-51-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,604,622 control chromosomes in the GnomAD database, including 4,920 homozygotes. 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 0.075 ( 487 hom., cov: 32)
Exomes 𝑓: 0.076 ( 4433 hom. )
Consequence
PMEL
NM_006928.5 intron
NM_006928.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.103
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMEL | NM_006928.5 | c.-51-32G>A | intron_variant | NP_008859.1 | ||||
PMEL | NM_001200054.1 | c.-83G>A | upstream_gene_variant | NP_001186983.1 | ||||
PMEL | NM_001320121.1 | c.-83G>A | upstream_gene_variant | NP_001307050.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548493.5 | c.-51-32G>A | intron_variant | 2 | ENSP00000447374.1 | |||||
PMEL | ENST00000552882.5 | c.-51-32G>A | intron_variant | 5 | ENSP00000449690.1 | |||||
PMEL | ENST00000549418.5 | c.-51-32G>A | intron_variant | 4 | ENSP00000446633.1 |
Frequencies
GnomAD3 genomes AF: 0.0746 AC: 11347AN: 152162Hom.: 486 Cov.: 32
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GnomAD4 exome AF: 0.0760 AC: 110376AN: 1452342Hom.: 4433 Cov.: 30 AF XY: 0.0750 AC XY: 54209AN XY: 722314
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GnomAD4 genome AF: 0.0745 AC: 11348AN: 152280Hom.: 487 Cov.: 32 AF XY: 0.0737 AC XY: 5491AN XY: 74456
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
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