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GeneBe

7-69599742-T-G

Variant summary

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

The NM_015570.4(AUTS2):c.89T>G(p.Leu30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

AUTS2
NM_015570.4 missense

Scores

1
2
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.993
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]

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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=0.20940802).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.89T>G p.Leu30Arg missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.89T>G p.Leu30Arg missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.89T>G p.Leu30Arg missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.89T>G p.Leu30Arg missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.89T>G p.Leu30Arg missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 03, 2023The c.89T>G (p.L30R) alteration is located in exon 1 (coding exon 1) of the AUTS2 gene. This alteration results from a T to G substitution at nucleotide position 89, causing the leucine (L) at amino acid position 30 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Pathogenic
26
DANN
Uncertain
0.99
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.018
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.50
T;T;T;T
M_CAP
Uncertain
0.29
D
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.99
N;N;N
PrimateAI
Pathogenic
0.93
D
Polyphen
0.83
.;P;P;.
Vest4
0.10, 0.088, 0.063
MutPred
0.36
Gain of methylation at L30 (P = 6e-04);Gain of methylation at L30 (P = 6e-04);Gain of methylation at L30 (P = 6e-04);Gain of methylation at L30 (P = 6e-04);
MVP
0.068
MPC
3.3
ClinPred
0.61
D
GERP RS
3.7
Varity_R
0.33
gMVP
0.050

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: chr7-69064728; API