chr16-89268541-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP4
The NM_013275.6(ANKRD11):c.7929G>C(p.Glu2643Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,493,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E2643K) has been classified as Uncertain significance.
Frequency
Consequence
NM_013275.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.7929G>C | p.Glu2643Asp | missense_variant | 13/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.7929G>C | p.Glu2643Asp | missense_variant | 14/14 | ||
ANKRD11 | NM_001256183.2 | c.7929G>C | p.Glu2643Asp | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.7929G>C | p.Glu2643Asp | missense_variant | 13/13 | 5 | NM_013275.6 | P1 | |
ENST00000602042.1 | n.438C>G | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000666 AC: 1AN: 150200Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.00000659 AC: 1AN: 151828Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 80880
GnomAD4 exome AF: 0.0000238 AC: 32AN: 1342854Hom.: 0 Cov.: 22 AF XY: 0.0000211 AC XY: 14AN XY: 662942
GnomAD4 genome ? AF: 0.00000666 AC: 1AN: 150200Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 73240
ClinVar
Submissions by phenotype
KBG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 16, 2023 | ClinVar contains an entry for this variant (Variation ID: 1761253). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ANKRD11 protein function. 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. This variant has not been reported in the literature in individuals affected with ANKRD11-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 2643 of the ANKRD11 protein (p.Glu2643Asp). This variant is present in population databases (rs779813123, gnomAD 0.002%). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2018 | The p.E2643D variant (also known as c.7929G>C), located in coding exon 11 of the ANKRD11 gene, results from a G to C substitution at nucleotide position 7929. The glutamic acid at codon 2643 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at