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GeneBe

7-69599664-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015570(AUTS2):c.11C>T(p.Pro4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00289 in 152036 control chromosomes in the gnomAD Genomes database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 1 hom. )

Consequence

AUTS2
NM_015570 missense

Scores

1
4
7

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.82

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.0038175583).
BP6
?
Variant 7:69599664-C>T is Benign according to our data. Variant chr7-69599664-C-T is described in ClinVar as [Benign]. Clinvar id is 975656. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-69599664-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected. gnomad allele frequency = 0.00289 (440/152036) while in subpopulation NFE AF= 0.00512 (348/67974). AF 95% confidence interval is 0.00468. There are 2 homozygotes in gnomad. There are 177 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 440 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.11C>T p.Pro4Leu missense_variant 1/19 A1

Frequencies

GnomAD3 genomes
AF:
0.00289
AC:
440
AN:
152036
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000845
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000660
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.00512
Gnomad OTH
AF:
0.00384
GnomAD3 exomes
AF:
0.00341
AC:
38
AN:
11154
Hom.:
1
AF XY:
0.00368
AC XY:
22
AN XY:
5974
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00610
Gnomad ASJ exome
AF:
0.0101
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000211
Gnomad NFE exome
AF:
0.00609
Gnomad OTH exome
AF:
0.0155
GnomAD4 exome
AF:
0.00483
AC:
5563
AN:
1152222
Hom.:
22
AF XY:
0.00471
AC XY:
2610
AN XY:
554422
show subpopulations
Gnomad4 AFR exome
AF:
0.000990
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.00533
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000280
Gnomad4 FIN exome
AF:
0.000544
Gnomad4 NFE exome
AF:
0.00546
Gnomad4 OTH exome
AF:
0.00335
Alfa
AF:
0.00434
Hom.:
0
Bravo
AF:
0.00296
ExAC
AF:
0.000722
AC:
22
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Benign, criteria provided, single submitterclinical testingInstitute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-NürnbergMar 21, 2023This variant has been identified by standard clinical testing. -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023Criteria applied: PP2, BS1, BS2 -
Benign, criteria provided, single submitterclinical testingInvitaeOct 31, 2022- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 28, 2018- -
Intellectual disability Benign:1
Likely benign, no assertion criteria providedclinical testingCentre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de LilleJan 01, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.25
Cadd
Pathogenic
27
Dann
Uncertain
1.0
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.76
T;T;T;T
MetaRNN
Benign
0.0038
T;T;T;T
MetaSVM
Benign
-0.83
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.92
D
Polyphen
1.0
.;D;D;.
Vest4
0.38, 0.37, 0.47
MVP
0.47
MPC
2.6
ClinPred
0.067
T
GERP RS
3.6
Varity_R
0.25
gMVP
0.16

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: rs200189077; hg19: chr7-69064650; COSMIC: COSV61410988; COSMIC: COSV61410988;