chr12-55957041-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001384361.1(PMEL):c.1262C>G(p.Thr421Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,614,100 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.1262C>G | p.Thr421Arg | missense_variant | 6/11 | ENST00000548747.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548747.6 | c.1262C>G | p.Thr421Arg | missense_variant | 6/11 | 1 | NM_001384361.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000562 AC: 14AN: 249288Hom.: 0 AF XY: 0.0000593 AC XY: 8AN XY: 134940
GnomAD4 exome AF: 0.000153 AC: 223AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.000144 AC XY: 105AN XY: 727244
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2022 | The c.1262C>G (p.T421R) alteration is located in exon 6 (coding exon 6) of the PMEL gene. This alteration results from a C to G substitution at nucleotide position 1262, causing the threonine (T) at amino acid position 421 to be replaced by an arginine (R). 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