NM_015570.4:c.106G>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015570.4(AUTS2):c.106G>C(p.Gly36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,369,464 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G36S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.763

Publications

0 publications found

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]

AUTS2 Gene-Disease associations (from GenCC):

autism spectrum disorder due to AUTS2 deficiency
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2022962).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AUTS2	NM_015570.4	MANE Select	c.106G>C	p.Gly36Arg	missense	Exon 1 of 19	NP_056385.1	Q8WXX7-1
AUTS2	NM_001127231.3		c.106G>C	p.Gly36Arg	missense	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
AUTS2	NM_001127232.3		c.106G>C	p.Gly36Arg	missense	Exon 1 of 5	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.106G>C	p.Gly36Arg	missense	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
AUTS2	ENST00000406775.6	TSL:1	c.106G>C	p.Gly36Arg	missense	Exon 1 of 18	ENSP00000385263.2	Q8WXX7-2
AUTS2	ENST00000403018.3	TSL:1	c.106G>C	p.Gly36Arg	missense	Exon 1 of 5	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

34442

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.21e-7

AC:

AN:

1217918

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

594320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24150

American (AMR)

AF:

0.00

AC:

AN:

11466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17636

East Asian (EAS)

AF:

0.0000365

AC:

AN:

27432

South Asian (SAS)

AF:

0.00

AC:

AN:

47846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

996996

Other (OTH)

AF:

0.00

AC:

AN:

49444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41332

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67812

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

AUTS2-related disorder (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.76

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.36

REVEL

Benign

0.052

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

0.021

Vest4

0.24

MutPred

0.45

Gain of methylation at G36 (P = 0.001)

MVP

0.068

MPC

3.1

ClinPred

0.53

GERP RS

3.0

PromoterAI

0.066

Neutral

(source)

Varity_R

0.089

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over