rs199529123
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_012310.5(KIF4A):c.2183G>A(p.Arg728Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000572 in 1,188,099 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts 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. R728W) has been classified as Uncertain significance.
Frequency
Consequence
NM_012310.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF4A | NM_012310.5 | c.2183G>A | p.Arg728Gln | missense_variant | 20/31 | ENST00000374403.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF4A | ENST00000374403.4 | c.2183G>A | p.Arg728Gln | missense_variant | 20/31 | 1 | NM_012310.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000269 AC: 3AN: 111577Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1AN XY: 33771
GnomAD3 exomes AF: 0.0000683 AC: 10AN: 146470Hom.: 0 AF XY: 0.0000880 AC XY: 4AN XY: 45434
GnomAD4 exome AF: 0.0000604 AC: 65AN: 1076470Hom.: 0 Cov.: 30 AF XY: 0.0000542 AC XY: 19AN XY: 350528
GnomAD4 genome ? AF: 0.0000269 AC: 3AN: 111629Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1AN XY: 33833
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 | Aug 01, 2022 | Variant summary: KIF4A c.2183G>A (p.Arg728Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 146470 control chromosomes, including 4 hemizygotes (gnomAD). To our knowledge, no occurrence of c.2183G>A in individuals affected with Intellectual Disability, X-Linked 100 and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 15, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at