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GeneBe

7-69599771-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_015570(AUTS2):c.118G>A(p.Ala40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151794 control chromosomes in the gnomAD Genomes 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: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

AUTS2
NM_015570 missense

Scores

1
2
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.550

Links

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.0000264 (4/151794) while in subpopulation NFE AF= 0.0000589 (4/67896). AF 95% confidence interval is 0.0000197. There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0892635).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.118G>A p.Ala40Thr missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.118G>A p.Ala40Thr missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.118G>A p.Ala40Thr missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.118G>A p.Ala40Thr missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.118G>A p.Ala40Thr missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151794
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:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000217
AC:
2
AN:
92074
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
52120
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000609
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
17
AN:
1326420
Hom.:
0
AF XY:
0.0000138
AC XY:
9
AN XY:
653552
show subpopulations
Gnomad4 AFR exome
AF:
0.0000369
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:
0.0000134
Gnomad4 OTH exome
AF:
0.0000367
Alfa
AF:
0.0000587
Hom.:
0
Bravo
AF:
0.0000378

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 testingGeneDxMay 02, 2016The A40T variant in the AUTS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 4400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A40T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved mammals. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret A40T as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.64
Cadd
Benign
20
Dann
Uncertain
1.0
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.065
N
LIST_S2
Benign
0.54
T;T;T;T
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.089
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.86
D
Polyphen
0.0
.;B;B;.
Vest4
0.12, 0.10, 0.14
MutPred
0.29
Gain of phosphorylation at A40 (P = 0.0321);Gain of phosphorylation at A40 (P = 0.0321);Gain of phosphorylation at A40 (P = 0.0321);Gain of phosphorylation at A40 (P = 0.0321);
MVP
0.10
MPC
1.5
ClinPred
0.19
T
GERP RS
1.7
Varity_R
0.072
gMVP
0.059

Splicing

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: rs911513762; hg19: chr7-69064757;