12-55954267-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001384361.1(PMEL):c.1933T>A(p.Cys645Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001384361.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMEL | NM_001384361.1 | c.1933T>A | p.Cys645Ser | missense_variant | 11/11 | ENST00000548747.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548747.6 | c.1933T>A | p.Cys645Ser | missense_variant | 11/11 | 1 | NM_001384361.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251304Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135840
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461684Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727134
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74506
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 05, 2024 | The c.1954T>A (p.C652S) alteration is located in exon 11 (coding exon 11) of the PMEL gene. This alteration results from a T to A substitution at nucleotide position 1954, causing the cysteine (C) at amino acid position 652 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at