7-69599771-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate
The NM_015570(AUTS2):c.118G>A(p.Ala40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151794 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
AUTS2
NM_015570 missense
NM_015570 missense
Scores
1
2
10
Clinical Significance
Conservation
PhyloP100: 0.550
Links
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.0000264 (4/151794) while in subpopulation NFE AF= 0.0000589 (4/67896). AF 95% confidence interval is 0.0000197. There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0892635).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.118G>A | p.Ala40Thr | missense_variant | 1/19 | ENST00000342771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.118G>A | p.Ala40Thr | missense_variant | 1/19 | 1 | NM_015570.4 | P4 | |
AUTS2 | ENST00000406775.6 | c.118G>A | p.Ala40Thr | missense_variant | 1/18 | 1 | |||
AUTS2 | ENST00000403018.3 | c.118G>A | p.Ala40Thr | missense_variant | 1/5 | 1 | |||
AUTS2 | ENST00000644939.1 | c.118G>A | p.Ala40Thr | missense_variant | 1/19 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151794Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000217 AC: 2AN: 92074Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 52120
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2016 | The A40T variant in the AUTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 4400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A40T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved mammals. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret A40T as a variant of uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Pathogenic
D
Polyphen
0.0
.;B;B;.
Vest4
0.12, 0.10, 0.14
MutPred
Gain of phosphorylation at A40 (P = 0.0321);Gain of phosphorylation at A40 (P = 0.0321);Gain of phosphorylation at A40 (P = 0.0321);Gain of phosphorylation at A40 (P = 0.0321);
MVP
0.10
MPC
1.5
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at