12-55957045-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001384361.1(PMEL):c.1258A>C(p.Thr420Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMEL | NM_001384361.1 | c.1258A>C | p.Thr420Pro | missense_variant | 6/11 | ENST00000548747.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMEL | ENST00000548747.6 | c.1258A>C | p.Thr420Pro | missense_variant | 6/11 | 1 | NM_001384361.1 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249300Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134948
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461756Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727172
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2023 | The c.1258A>C (p.T420P) alteration is located in exon 6 (coding exon 6) of the PMEL gene. This alteration results from a A to C substitution at nucleotide position 1258, causing the threonine (T) at amino acid position 420 to be replaced by a proline (P). 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