7-69599703-G-T
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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
NM_015570.4 missense
Scores
5
4
10
Clinical Significance
Conservation
PhyloP100: 5.00
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. 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 |
---|---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.50G>T | p.Arg17Leu | missense_variant | 1/19 | 1 | NM_015570.4 | ENSP00000344087.4 | ||
AUTS2 | ENST00000406775.6 | c.50G>T | p.Arg17Leu | missense_variant | 1/18 | 1 | ENSP00000385263.2 | |||
AUTS2 | ENST00000403018.3 | c.50G>T | p.Arg17Leu | missense_variant | 1/5 | 1 | ENSP00000385572.2 | |||
AUTS2 | ENST00000644939.1 | c.50G>T | p.Arg17Leu | missense_variant | 1/19 | ENSP00000496726.1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151828Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1172992Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 567130
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151828Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74158
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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 submitter | clinical testing | GeneDx | Dec 18, 2024 | Has 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;L
MutationTaster
Benign
N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;N;D
REVEL
Benign
Sift
Pathogenic
.;D;D;D
Sift4G
Pathogenic
.;D;D;D
Polyphen
0.87
.;P;P;.
Vest4
0.35, 0.43
MutPred
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
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at