chr12-101099660-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001286615.2(ANO4):c.2089A>G(p.Lys697Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,611,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
ANO4
NM_001286615.2 missense
NM_001286615.2 missense
Scores
4
9
Clinical Significance
Conservation
PhyloP100: 5.19
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, ANO4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17321631).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO4 | NM_001286615.2 | c.2089A>G | p.Lys697Glu | missense_variant | 22/28 | ENST00000392977.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO4 | ENST00000392977.8 | c.2089A>G | p.Lys697Glu | missense_variant | 22/28 | 2 | NM_001286615.2 | ||
ANO4 | ENST00000644049.1 | c.2587A>G | p.Lys863Glu | missense_variant | 24/30 | ||||
ANO4 | ENST00000392979.7 | c.1984A>G | p.Lys662Glu | missense_variant | 21/27 | 2 | P1 | ||
ANO4 | ENST00000550015.1 | n.743A>G | non_coding_transcript_exon_variant | 9/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249284Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134696
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GnomAD4 exome AF: 0.0000158 AC: 23AN: 1459654Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 726074
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2023 | The c.1984A>G (p.K662E) alteration is located in exon 21 (coding exon 20) of the ANO4 gene. This alteration results from a A to G substitution at nucleotide position 1984, causing the lysine (K) at amino acid position 662 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
0.096, 0.0020
.;B;B
Vest4
0.45, 0.42
MutPred
0.43
.;.;Loss of ubiquitination at K697 (P = 0.0081);
MVP
0.043
MPC
1.0
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at