7-70790653-G-T

Position:

chr7-70790653-G-T

Variant summary

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

The NM_015570.4(AUTS2):c.3437G>T(p.Gly1146Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,613,212 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 11 hom., cov: 32)

Exomes 𝑓: 0.011 ( 108 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.26

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004080683).

BP6

Variant 7-70790653-G-T is Benign according to our data. Variant chr7-70790653-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 376956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-70790653-G-T is described in Lovd as [Benign]. Variant chr7-70790653-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00884 (1345/152198) while in subpopulation NFE AF= 0.0137 (932/68002). AF 95% confidence interval is 0.013. There are 11 homozygotes in gnomad4. There are 647 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1345 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4 linkuse as main transcript	c.3437G>T	p.Gly1146Val	missense_variant	19/19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10 linkuse as main transcript	c.3437G>T	p.Gly1146Val	missense_variant	19/19	1	NM_015570.4	ENSP00000344087	P4	Q8WXX7-1

Frequencies

GnomAD3 genomes

AF:

0.00884

AC:

1345

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.00925

AC:

2262

AN:

244644

Hom.:

AF XY:

0.00924

AC XY:

1231

AN XY:

133278

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00528

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0110

AC:

16001

AN:

1461014

Hom.:

108

Cov.:

AF XY:

0.0109

AC XY:

7902

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00518

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00933

GnomAD4 genome

AF:

0.00884

AC:

1345

AN:

152198

Hom.:

Cov.:

AF XY:

0.00869

AC XY:

647

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.0161

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00726

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.0103

AC:

1255

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	AUTS2: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.029

.;.;T;.;.;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.88

D;D;D;D;D;D;D

MetaRNN

Benign

0.0041

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;.;N;.;.;.;.

MutationTaster

Benign

0.84

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.88

.;N;N;.;.;.;.

REVEL

Benign

0.050

Sift

Benign

0.32

.;T;T;.;.;.;.

Sift4G

Benign

0.64

.;T;T;.;.;T;T

Polyphen

0.35

.;B;B;.;.;.;.

Vest4

0.19, 0.13

MPC

0.54

ClinPred

0.0042

GERP RS

2.6

Varity_R

0.11

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over