chr19-757373-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_173481.4(MISP):c.427C>T(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,078 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. R143H) has been classified as Uncertain significance.
Frequency
Consequence
NM_173481.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MISP | NM_173481.4 | c.427C>T | p.Arg143Cys | missense_variant | Exon 2 of 5 | ENST00000215582.8 | NP_775752.1 | |
MISP | XM_011527685.3 | c.427C>T | p.Arg143Cys | missense_variant | Exon 2 of 5 | XP_011525987.1 | ||
MISP | XM_011527686.3 | c.427C>T | p.Arg143Cys | missense_variant | Exon 2 of 5 | XP_011525988.1 | ||
MISP | NR_135168.2 | n.61-2536C>T | intron_variant | Intron 1 of 3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000494 AC: 12AN: 242936Hom.: 0 AF XY: 0.0000605 AC XY: 8AN XY: 132148
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1459818Hom.: 0 Cov.: 33 AF XY: 0.0000413 AC XY: 30AN XY: 726138
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74446
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.427C>T (p.R143C) alteration is located in exon 2 (coding exon 1) of the MISP gene. This alteration results from a C to T substitution at nucleotide position 427, causing the arginine (R) at amino acid position 143 to be replaced by a cysteine (C). 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