chr16-89268491-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_013275.6(ANKRD11):c.7979T>C(p.Leu2660Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 27)
Consequence
ANKRD11
NM_013275.6 missense
NM_013275.6 missense
Scores
8
8
2
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;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.814
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.7979T>C | p.Leu2660Ser | missense_variant | 13/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.7979T>C | p.Leu2660Ser | missense_variant | 14/14 | ||
ANKRD11 | NM_001256183.2 | c.7979T>C | p.Leu2660Ser | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.7979T>C | p.Leu2660Ser | missense_variant | 13/13 | 5 | NM_013275.6 | P1 | |
ENST00000602042.1 | n.388A>G | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 27
GnomAD3 genomes
?
Cov.:
27
GnomAD4 exome Cov.: 17
GnomAD4 exome
Cov.:
17
GnomAD4 genome ? Cov.: 27
GnomAD4 genome
?
Cov.:
27
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Global developmental delay Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University Hospital Muenster | Aug 17, 2022 | ACMG categories: PM2,PP3,BP1 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.
Sift4G
Pathogenic
D;D;.;.
Polyphen
D;D;.;D
Vest4
MutPred
Gain of disorder (P = 0.0066);Gain of disorder (P = 0.0066);.;Gain of disorder (P = 0.0066);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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.