rs369869329
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_013275.6(ANKRD11):c.3418G>A(p.Ala1140Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_013275.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD11 | NM_013275.6 | c.3418G>A | p.Ala1140Thr | missense_variant | 9/13 | ENST00000301030.10 | |
ANKRD11 | NM_001256182.2 | c.3418G>A | p.Ala1140Thr | missense_variant | 10/14 | ||
ANKRD11 | NM_001256183.2 | c.3418G>A | p.Ala1140Thr | missense_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD11 | ENST00000301030.10 | c.3418G>A | p.Ala1140Thr | missense_variant | 9/13 | 5 | NM_013275.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251250Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135790
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461762Hom.: 0 Cov.: 37 AF XY: 0.0000138 AC XY: 10AN XY: 727198
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74424
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 07, 2016 | - - |
KBG syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2021 | This sequence change replaces alanine with threonine at codon 1140 of the ANKRD11 protein (p.Ala1140Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. 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. 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. ClinVar contains an entry for this variant (Variation ID: 434199). This variant has not been reported in the literature in individuals affected with ANKRD11-related conditions. This variant is present in population databases (rs369869329, ExAC no frequency). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2022 | The c.3418G>A (p.A1140T) alteration is located in exon 9 (coding exon 7) of the ANKRD11 gene. This alteration results from a G to A substitution at nucleotide position 3418, causing the alanine (A) at amino acid position 1140 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
ANKRD11-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 14, 2024 | The ANKRD11 c.3418G>A variant is predicted to result in the amino acid substitution p.Ala1140Thr. To our knowledge, this variant has not been reported in the literature. This variant has been reported in 2 heterozygous individuals of unknown phenotype in the "Other" subpopulation in the gnomAD database. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at