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GeneBe

7-69599765-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015570.4(AUTS2):c.112G>T(p.Gly38Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000886 in 1,241,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

1
2
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.724
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.12754384).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.112G>T p.Gly38Cys missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.112G>T p.Gly38Cys missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.112G>T p.Gly38Cys missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.112G>T p.Gly38Cys missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.112G>T p.Gly38Cys missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000202
AC:
1
AN:
49570
Hom.:
0
AF XY:
0.0000339
AC XY:
1
AN XY:
29486
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000113
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000886
AC:
11
AN:
1241944
Hom.:
0
Cov.:
32
AF XY:
0.00000987
AC XY:
6
AN XY:
608152
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:
0.000207
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000109
AC:
1

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 submitterclinical testingInvitaeAug 23, 2022Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with AUTS2-related conditions. This variant is present in population databases (rs752423410, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 38 of the AUTS2 protein (p.Gly38Cys). 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.45
Cadd
Benign
22
Dann
Uncertain
0.98
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.55
T;T;T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.13
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.89
D
Polyphen
0.90
.;P;P;.
Vest4
0.27, 0.25, 0.26
MutPred
0.40
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP
0.17
MPC
2.0
ClinPred
0.28
T
GERP RS
1.5
Varity_R
0.11
gMVP
0.085

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752423410; hg19: chr7-69064751; API