rs386134124
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_000096.4(CP):c.587C>T(p.Pro196Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P196R) has been classified as Pathogenic.
Frequency
Consequence
NM_000096.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CP | NM_000096.4 | c.587C>T | p.Pro196Leu | missense_variant | 3/19 | ENST00000264613.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CP | ENST00000264613.11 | c.587C>T | p.Pro196Leu | missense_variant | 3/19 | 1 | NM_000096.4 | P1 | |
CP | ENST00000490639.5 | n.619C>T | non_coding_transcript_exon_variant | 3/17 | 1 | ||||
CP | ENST00000481169.5 | c.587C>T | p.Pro196Leu | missense_variant, NMD_transcript_variant | 3/18 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251344Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135836
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461732Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727168
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 09, 2024 | Variant summary: CP c.587C>T (p.Pro196Leu) results in a non-conservative amino acid change located in the Multicopper oxidase-like, N-terminal domain (IPR011707) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251344 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.587C>T in individuals affected with Neurodegeneration With Brain Iron Accumulation/Aceruloplasminaemia and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at