7-69599703-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015570.4(AUTS2):​c.50G>T​(p.Arg17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000659 in 151,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AUTS2
NM_015570.4 missense

Scores

5
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.50G>T p.Arg17Leu 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.50G>T p.Arg17Leu missense_variant 1/191 NM_015570.4 ENSP00000344087.4 Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.50G>T p.Arg17Leu missense_variant 1/181 ENSP00000385263.2 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.50G>T p.Arg17Leu missense_variant 1/51 ENSP00000385572.2 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.50G>T p.Arg17Leu missense_variant 1/19 ENSP00000496726.1 A0A2R8Y8C6

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151828
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1172992
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
567130
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
AF:
0.00000659
AC:
1
AN:
151828
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74158
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Gnomad4 OTH
AF:
0.00

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 testingGeneDxDec 18, 2024Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Benign
0.0047
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
.;.;T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Pathogenic
0.90
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
1.1
.;L;L;L
MutationTaster
Benign
0.76
N;N;N
PrimateAI
Pathogenic
0.97
D
PROVEAN
Benign
-1.3
.;N;N;D
REVEL
Benign
0.15
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Pathogenic
0.0
.;D;D;D
Polyphen
0.87
.;P;P;.
Vest4
0.35, 0.43
MutPred
0.36
Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);
MVP
0.45
MPC
2.4
ClinPred
0.91
D
GERP RS
3.7
Varity_R
0.25
gMVP
0.31

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: rs1792261573; hg19: chr7-69064689; API