chr15-40987186-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting
The NM_017553.3(INO80):c.3737G>A(p.Arg1246Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,602,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Consequence
NM_017553.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INO80 | NM_017553.3 | c.3737G>A | p.Arg1246Gln | missense_variant | Exon 31 of 36 | ENST00000648947.1 | NP_060023.1 | |
INO80 | XM_047432698.1 | c.3737G>A | p.Arg1246Gln | missense_variant | Exon 31 of 36 | XP_047288654.1 | ||
INO80 | XM_011521686.4 | c.1787G>A | p.Arg596Gln | missense_variant | Exon 17 of 22 | XP_011519988.1 | ||
INO80 | NR_104038.2 | n.3960G>A | non_coding_transcript_exon_variant | Exon 30 of 35 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000785 AC: 119AN: 151572Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000306 AC: 77AN: 251224Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135804
GnomAD4 exome AF: 0.000152 AC: 220AN: 1450436Hom.: 0 Cov.: 26 AF XY: 0.000122 AC XY: 88AN XY: 722404
GnomAD4 genome AF: 0.000784 AC: 119AN: 151690Hom.: 0 Cov.: 32 AF XY: 0.000782 AC XY: 58AN XY: 74190
ClinVar
Submissions by phenotype
INO80-related immunodeficiency Pathogenic:1
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.035%). Predicted Consequence/Location: Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.72 (>=0.6, sensitivity 0.68 and specificity 0.92)]. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with INO80 related disorder (ClinVar ID: VCV000183320 /PMID: 25558065).The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25558065). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. -
Seizure;C2677180:Primary microcephaly;C3714756:Intellectual disability Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at