rs143679158
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_015570.4(AUTS2):āc.1247A>Gā(p.Gln416Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000165 in 816,374 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 30)
Exomes š: 0.00018 ( 0 hom. )
Consequence
AUTS2
NM_015570.4 missense
NM_015570.4 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 6.22
Genes affected
AUTS2 (HGNC:14262): (activator of transcription and developmental regulator AUTS2) This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.064305186).
BP6
?
Variant 7-70764784-A-G is Benign according to our data. Variant chr7-70764784-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 547994.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS2
?
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.1247A>G | p.Gln416Arg | missense_variant | 8/19 | ENST00000342771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.1247A>G | p.Gln416Arg | missense_variant | 8/19 | 1 | NM_015570.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 151148Hom.: 0 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
17
AN:
151148
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000130 AC: 20AN: 153802Hom.: 0 AF XY: 0.000135 AC XY: 11AN XY: 81276
GnomAD3 exomes
AF:
AC:
20
AN:
153802
Hom.:
AF XY:
AC XY:
11
AN XY:
81276
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000177 AC: 118AN: 665108Hom.: 0 Cov.: 9 AF XY: 0.000210 AC XY: 74AN XY: 352780
GnomAD4 exome
AF:
AC:
118
AN:
665108
Hom.:
Cov.:
9
AF XY:
AC XY:
74
AN XY:
352780
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 151266Hom.: 0 Cov.: 30 AF XY: 0.0000541 AC XY: 4AN XY: 73912
GnomAD4 genome
?
AF:
AC:
17
AN:
151266
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
73912
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
3
ExAC
?
AF:
AC:
9
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 416 of the AUTS2 protein (p.Gln416Arg). This variant is present in population databases (rs143679158, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. 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: 547994). 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 AUTS2 protein function with a negative predictive value of 80%. 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. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2020 | - - |
Autism spectrum disorder due to AUTS2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 08, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
0.95
.;P;P;.;.
Vest4
0.45, 0.35
MVP
0.33
MPC
0.78
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at