chr12-55955270-T-TTACCTATATATATATATA
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_001384361.1(PMEL):c.1850+3_1850+4insTATATATATATATAGGTA variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,600,952 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0058 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 3 hom. )
Consequence
PMEL
NM_001384361.1 splice_donor_region, intron
NM_001384361.1 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.160
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.
BP6
?
Variant 12-55955270-T-TTACCTATATATATATATA is Benign according to our data. Variant chr12-55955270-T-TTACCTATATATATATATA is described in ClinVar as [Benign]. Clinvar id is 781077.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00579 (882/152258) while in subpopulation AFR AF= 0.0205 (853/41522). AF 95% confidence interval is 0.0194. There are 8 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMEL | NM_001384361.1 | c.1850+3_1850+4insTATATATATATATAGGTA | splice_donor_region_variant, intron_variant | ENST00000548747.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548747.6 | c.1850+3_1850+4insTATATATATATATAGGTA | splice_donor_region_variant, intron_variant | 1 | NM_001384361.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00580 AC: 882AN: 152140Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.000760 AC: 191AN: 251200Hom.: 0 AF XY: 0.000589 AC XY: 80AN XY: 135814
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GnomAD4 exome AF: 0.000544 AC: 788AN: 1448694Hom.: 3 Cov.: 28 AF XY: 0.000462 AC XY: 333AN XY: 721516
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GnomAD4 genome ? AF: 0.00579 AC: 882AN: 152258Hom.: 8 Cov.: 32 AF XY: 0.00571 AC XY: 425AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2018 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at