rs755428630
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PM4_SupportingBS2
The NM_014423.4(AFF4):c.516_518dupACA(p.Glu172_His173insGln) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000192 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014423.4 disruptive_inframe_insertion
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 |
---|---|---|---|---|---|---|---|---|
AFF4 | NM_014423.4 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 21 | ENST00000265343.10 | NP_055238.1 | |
AFF4 | XM_005271963.6 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 4 of 22 | XP_005272020.1 | ||
AFF4 | XM_006714587.5 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 20 | XP_006714650.1 | ||
AFF4 | XM_047417103.1 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 4 of 21 | XP_047273059.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AFF4 | ENST00000265343.10 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 21 | 1 | NM_014423.4 | ENSP00000265343.5 | ||
AFF4 | ENST00000378595.7 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 13 | 1 | ENSP00000367858.3 | |||
AFF4 | ENST00000465484.1 | n.775_777dupACA | non_coding_transcript_exon_variant | Exon 3 of 5 | 1 | |||||
AFF4 | ENST00000491831.5 | n.776_778dupACA | non_coding_transcript_exon_variant | Exon 3 of 7 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461890Hom.: 1 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727244
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome Uncertain:1
This variant, c.516_518dup, results in the insertion of 1 amino acid(s) of the AFF4 protein (p.Glu172_His173insGln), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AFF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 591050). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at