7-123479947-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_178827.5(IQUB):c.1258C>T(p.Arg420Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,608,834 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R420H) has been classified as Uncertain significance.
Frequency
Consequence
NM_178827.5 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 |
---|---|---|---|---|---|---|---|
IQUB | NM_178827.5 | c.1258C>T | p.Arg420Cys | missense_variant | 8/13 | ENST00000324698.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQUB | ENST00000324698.11 | c.1258C>T | p.Arg420Cys | missense_variant | 8/13 | 1 | NM_178827.5 | P1 | |
IQUB | ENST00000466202.5 | c.1258C>T | p.Arg420Cys | missense_variant | 8/13 | 1 | P1 | ||
IQUB | ENST00000484508.5 | c.1258C>T | p.Arg420Cys | missense_variant, NMD_transcript_variant | 8/14 | 2 | |||
IQUB | ENST00000469057.1 | c.1235-10563C>T | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000613 AC: 15AN: 244794Hom.: 0 AF XY: 0.0000833 AC XY: 11AN XY: 132128
GnomAD4 exome AF: 0.000260 AC: 379AN: 1456782Hom.: 0 Cov.: 31 AF XY: 0.000275 AC XY: 199AN XY: 724566
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74258
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2023 | The c.1258C>T (p.R420C) alteration is located in exon 8 (coding exon 7) of the IQUB gene. This alteration results from a C to T substitution at nucleotide position 1258, causing the arginine (R) at amino acid position 420 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