7-69599744-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015570.4(AUTS2):​c.91G>A​(p.Gly31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000833 in 1,199,976 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27537096).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.91G>A p.Gly31Arg missense_variant 1/19 ENST00000342771.10 NP_056385.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.91G>A p.Gly31Arg missense_variant 1/191 NM_015570.4 ENSP00000344087 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.91G>A p.Gly31Arg missense_variant 1/181 ENSP00000385263 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.91G>A p.Gly31Arg missense_variant 1/51 ENSP00000385572 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.91G>A p.Gly31Arg missense_variant 1/19 ENSP00000496726 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.33e-7
AC:
1
AN:
1199976
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
583256
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autism spectrum disorder due to AUTS2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityMay 05, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
.;.;T;.
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.63
T;T;T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.28
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
.;N;N;N
MutationTaster
Benign
0.65
N;N;N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-0.16
.;N;N;N
REVEL
Benign
0.15
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Benign
0.079
.;T;T;T
Polyphen
0.93
.;P;P;.
Vest4
0.12, 0.11, 0.10
MutPred
0.20
Gain of methylation at G31 (P = 0.0033);Gain of methylation at G31 (P = 0.0033);Gain of methylation at G31 (P = 0.0033);Gain of methylation at G31 (P = 0.0033);
MVP
0.13
MPC
3.1
ClinPred
0.70
D
GERP RS
3.7
Varity_R
0.11
gMVP
0.050

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-69064730; API