Menu
GeneBe

7-69599681-C-G

Variant summary

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

The NM_015570.4(AUTS2):c.28C>G(p.Leu10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AUTS2
NM_015570.4 missense

Scores

2
1
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
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 Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15830332).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.28C>G p.Leu10Val missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1174916
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
568156
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:
0.00
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

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxJan 08, 2021Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
Cadd
Uncertain
25
Dann
Uncertain
0.99
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.028
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.76
T;T;T;T
M_CAP
Pathogenic
0.33
D
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.99
N;N;N
PrimateAI
Pathogenic
0.93
D
Polyphen
0.36
.;B;B;.
Vest4
0.15, 0.18, 0.11
MutPred
0.28
Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);
MVP
0.10
MPC
2.3
ClinPred
0.62
D
GERP RS
3.6
Varity_R
0.098
gMVP
0.073

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: chr7-69064667; API