chr16-89268527-TAGA-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_013275.6(ANKRD11):c.7940_7942del(p.Phe2647del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 29)
Consequence
ANKRD11
NM_013275.6 inframe_deletion
NM_013275.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.26
Genes affected
ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a region_of_interest Important for protein degradation (size 294) in uniprot entity ANR11_HUMAN there are 35 pathogenic changes around while only 4 benign (90%) in NM_013275.6
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_013275.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.7940_7942del | p.Phe2647del | inframe_deletion | 13/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.7940_7942del | p.Phe2647del | inframe_deletion | 14/14 | ||
ANKRD11 | NM_001256183.2 | c.7940_7942del | p.Phe2647del | inframe_deletion | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.7940_7942del | p.Phe2647del | inframe_deletion | 13/13 | 5 | NM_013275.6 | P1 | |
ENST00000602042.1 | n.427_429del | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2022 | In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; De novo variant with confirmed parentage; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.