Genetic Variant AUTS2:p.Gly9Ala (chr7-69599679-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015570.4(AUTS2):c.26G>C(p.Gly9Ala) variant causes a missense change involving the alteration of a 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

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), G2P, Orphanet
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3942241).

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.26G>C	p.Gly9Ala	missense	Exon 1 of 19	NP_056385.1	Q8WXX7-1
AUTS2	NM_001127231.3		c.26G>C	p.Gly9Ala	missense	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
AUTS2	NM_001127232.3		c.26G>C	p.Gly9Ala	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.26G>C	p.Gly9Ala	missense	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
AUTS2	ENST00000406775.6	TSL:1	c.26G>C	p.Gly9Ala	missense	Exon 1 of 18	ENSP00000385263.2	Q8WXX7-2
AUTS2	ENST00000403018.3	TSL:1	c.26G>C	p.Gly9Ala	missense	Exon 1 of 5	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1174524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

567956

African (AFR)

AF:

0.00

AC:

AN:

23510

American (AMR)

AF:

0.00

AC:

AN:

10230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16158

East Asian (EAS)

AF:

0.00

AC:

AN:

27244

South Asian (SAS)

AF:

0.00

AC:

AN:

36512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3204

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

974942

Other (OTH)

AF:

0.00

AC:

AN:

47688

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.1

PhyloP100

7.4

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.51

REVEL

Benign

0.094

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.045

Polyphen

0.30

Vest4

0.28

MutPred

0.28

Gain of helix (P = 0.0078)

MVP

0.42

MPC

2.8

ClinPred

0.96

GERP RS

3.6

PromoterAI

-0.092

Neutral

(source)

Varity_R

0.30

gMVP

0.11

Mutation Taster

=69/31

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over