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GeneBe

7-69599717-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM2_SupportingBP4

The NM_015570(AUTS2):c.64C>T(p.Arg22Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes 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 missense

Scores

3
4
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Links

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39417452).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.64C>T p.Arg22Trp missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.64C>T p.Arg22Trp missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.64C>T p.Arg22Trp missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.64C>T p.Arg22Trp missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.64C>T p.Arg22Trp missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000111
AC:
13
AN:
1173092
Hom.:
0
AF XY:
0.00000881
AC XY:
5
AN XY:
567314
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000123
Gnomad4 OTH exome
AF:
0.0000210

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 testingGeneDxApr 20, 2022Not 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; This variant is associated with the following publications: (PMID: 27535533) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.37
Cadd
Pathogenic
32
Dann
Uncertain
1.0
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Pathogenic
0.88
D
MetaRNN
Benign
0.39
T;T;T;T
MetaSVM
Benign
-0.66
T
MutationTaster
Benign
0.65
D;D;D
PrimateAI
Pathogenic
0.98
D
Polyphen
1.0
.;D;D;.
Vest4
0.28, 0.28, 0.47
MutPred
0.29
Loss of methylation at R27 (P = 0.0258);Loss of methylation at R27 (P = 0.0258);Loss of methylation at R27 (P = 0.0258);Loss of methylation at R27 (P = 0.0258);
MVP
0.29
MPC
2.6
ClinPred
0.96
D
GERP RS
3.7
Varity_R
0.19
gMVP
0.22

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: rs1263138285; hg19: chr7-69064703;