16-89268525-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PP5_ModerateBP4
The NM_013275.6(ANKRD11):c.7945G>A(p.Val2649Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 7.7e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ANKRD11
NM_013275.6 missense
NM_013275.6 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 4.95
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;
PP5
?
Variant 16-89268525-C-T is Pathogenic according to our data. Variant chr16-89268525-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1301284.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.41783652).. Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.7945G>A | p.Val2649Met | missense_variant | 13/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.7945G>A | p.Val2649Met | missense_variant | 14/14 | ||
ANKRD11 | NM_001256183.2 | c.7945G>A | p.Val2649Met | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.7945G>A | p.Val2649Met | missense_variant | 13/13 | 5 | NM_013275.6 | P1 | |
ENST00000602042.1 | n.422C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.67e-7 AC: 1AN: 1304188Hom.: 0 Cov.: 20 AF XY: 0.00000155 AC XY: 1AN XY: 645996
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1304188
Hom.:
Cov.:
20
AF XY:
AC XY:
1
AN XY:
645996
Gnomad4 AFR exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 06, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;N;.;.
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.
Sift4G
Uncertain
D;D;.;.
Polyphen
D;D;.;D
Vest4
MutPred
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;Loss of sheet (P = 0.0181);
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.