12-55957274-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001384361.1(PMEL):c.1029A>G(p.Ala343=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,018 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )
Consequence
PMEL
NM_001384361.1 synonymous
NM_001384361.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.661
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 -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 12-55957274-T-C is Benign according to our data. Variant chr12-55957274-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 739674.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.661 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMEL | NM_001384361.1 | c.1029A>G | p.Ala343= | synonymous_variant | 6/11 | ENST00000548747.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548747.6 | c.1029A>G | p.Ala343= | synonymous_variant | 6/11 | 1 | NM_001384361.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000159 AC: 40AN: 250818Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135508
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GnomAD4 exome AF: 0.000282 AC: 412AN: 1460788Hom.: 0 Cov.: 32 AF XY: 0.000274 AC XY: 199AN XY: 726480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 28, 2018 | - - |
Computational scores
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Benign
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Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at