7-69599747-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.94G>A(p.Ala32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
AUTS2
NM_015570 missense
NM_015570 missense
Scores
1
1
11
Clinical Significance
Conservation
PhyloP100: 2.24
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, Median coverage is 32.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11211595).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.94G>A | p.Ala32Thr | missense_variant | 1/19 | ENST00000342771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.94G>A | p.Ala32Thr | missense_variant | 1/19 | 1 | NM_015570.4 | P4 | |
AUTS2 | ENST00000406775.6 | c.94G>A | p.Ala32Thr | missense_variant | 1/18 | 1 | |||
AUTS2 | ENST00000403018.3 | c.94G>A | p.Ala32Thr | missense_variant | 1/5 | 1 | |||
AUTS2 | ENST00000644939.1 | c.94G>A | p.Ala32Thr | missense_variant | 1/19 | A1 |
Frequencies
GnomAD3 genomesCov.: 32
GnomAD3 genomes
Cov.:
32
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 | Invitae | Oct 04, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 32 of the AUTS2 protein (p.Ala32Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AUTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1412198). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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
0.18, 0.16, 0.17
MutPred
Gain of phosphorylation at A32 (P = 0.0207);Gain of phosphorylation at A32 (P = 0.0207);Gain of phosphorylation at A32 (P = 0.0207);Gain of phosphorylation at A32 (P = 0.0207);
MVP
0.16
MPC
1.5
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.