7-69599679-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015570.4(AUTS2):c.26G>A(p.Gly9Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 1,174,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000026 ( 0 hom. )
Consequence
AUTS2
NM_015570.4 missense
NM_015570.4 missense
Scores
3
5
5
Clinical Significance
Conservation
PhyloP100: 7.43
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.26G>A | p.Gly9Glu | missense_variant | 1/19 | ENST00000342771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.26G>A | p.Gly9Glu | missense_variant | 1/19 | 1 | NM_015570.4 | P4 | |
AUTS2 | ENST00000406775.6 | c.26G>A | p.Gly9Glu | missense_variant | 1/18 | 1 | |||
AUTS2 | ENST00000403018.3 | c.26G>A | p.Gly9Glu | missense_variant | 1/5 | 1 | |||
AUTS2 | ENST00000644939.1 | c.26G>A | p.Gly9Glu | missense_variant | 1/19 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000255 AC: 3AN: 1174524Hom.: 0 Cov.: 32 AF XY: 0.00000176 AC XY: 1AN XY: 567956
GnomAD4 exome
AF:
AC:
3
AN:
1174524
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
567956
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 ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.26G>A (p.G9E) alteration is located in exon 1 (coding exon 1) of the AUTS2 gene. This alteration results from a G to A substitution at nucleotide position 26, causing the glycine (G) at amino acid position 9 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
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Polyphen
0.43
.;B;B;.
Vest4
0.32, 0.34, 0.41
MutPred
Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP
0.26
MPC
3.3
ClinPred
D
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
Publications
No publications associated with this variant yet.