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GeneBe

7-69599759-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015570.4(AUTS2):c.106G>C(p.Gly36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,369,464 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 (★). Synonymous variant affecting the same amino acid position (i.e. G36G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

2
1
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763
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 Uncertain_significance.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2022962).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.106G>C p.Gly36Arg missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.106G>C p.Gly36Arg missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.106G>C p.Gly36Arg missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.106G>C p.Gly36Arg missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.106G>C p.Gly36Arg missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151546
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
8.21e-7
AC:
1
AN:
1217918
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
594320
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000365
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151546
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74016
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsJun 29, 2023The c.106G>C (p.G36R) alteration is located in exon 1 (coding exon 1) of the AUTS2 gene. This alteration results from a G to C substitution at nucleotide position 106, causing the glycine (G) at amino acid position 36 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
Cadd
Uncertain
24
Dann
Uncertain
1.0
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.65
T;T;T;T
M_CAP
Pathogenic
0.30
D
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.98
N;N;N
PrimateAI
Pathogenic
0.90
D
Polyphen
0.021
.;B;B;.
Vest4
0.24, 0.24, 0.23
MutPred
0.45
Gain of methylation at G36 (P = 0.001);Gain of methylation at G36 (P = 0.001);Gain of methylation at G36 (P = 0.001);Gain of methylation at G36 (P = 0.001);
MVP
0.068
MPC
3.1
ClinPred
0.53
D
GERP RS
3.0
Varity_R
0.089
gMVP
0.12

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: rs934214411; hg19: chr7-69064745; API