7-69599726-C-T

Variant summary

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

The NM_015570.4(AUTS2):​c.73C>T​(p.Arg25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,172,330 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

5
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2591434).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AUTS2NM_015570.4 linkc.73C>T p.Arg25Cys missense_variant 1/19 ENST00000342771.10 NP_056385.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AUTS2ENST00000342771.10 linkc.73C>T p.Arg25Cys missense_variant 1/191 NM_015570.4 ENSP00000344087.4 Q8WXX7-1
AUTS2ENST00000406775.6 linkc.73C>T p.Arg25Cys missense_variant 1/181 ENSP00000385263.2 Q8WXX7-2
AUTS2ENST00000403018.3 linkc.73C>T p.Arg25Cys missense_variant 1/51 ENSP00000385572.2 Q8WXX7-3
AUTS2ENST00000644939.1 linkc.73C>T p.Arg25Cys missense_variant 1/19 ENSP00000496726.1 A0A2R8Y8C6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000171
AC:
2
AN:
1172330
Hom.:
0
Cov.:
32
AF XY:
0.00000353
AC XY:
2
AN XY:
566862
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000278
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000103
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 testingGeneDxAug 08, 2024Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.065
.;.;T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.48
N
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Pathogenic
0.63
D
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;L;L;L
PrimateAI
Pathogenic
0.98
D
PROVEAN
Benign
-1.1
.;N;N;D
REVEL
Benign
0.12
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Pathogenic
0.0010
.;D;D;D
Polyphen
0.21
.;B;B;.
Vest4
0.41, 0.43, 0.48
MutPred
0.28
Loss of methylation at R25 (P = 0.0239);Loss of methylation at R25 (P = 0.0239);Loss of methylation at R25 (P = 0.0239);Loss of methylation at R25 (P = 0.0239);
MVP
0.20
MPC
3.1
ClinPred
0.82
D
GERP RS
2.8
Varity_R
0.14
gMVP
0.25

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: chr7-69064712; API