7-70763034-G-T

Position:

• chr7-70763034-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015570.4(AUTS2):​c.907G>T​(p.Ala303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 1,613,978 control chromosomes in the GnomAD database, including 2,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.073 (559 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1987 hom.)
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0920

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015388131).
• BP6: Variant 7-70763034-G-T is Benign according to our data. Variant chr7-70763034-G-T is described in ClinVar as [Benign]. Clinvar id is 1253894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.907G>T	p.Ala303Ser	missense_variant	7/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.907G>T	p.Ala303Ser	missense_variant	7/19	1	NM_015570.4	P4

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11094 AN: 151982 Hom.: 557 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0754

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.00519

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0892

GnomAD3 exomes AF: 0.0536 AC: 13469 AN: 251406 Hom.: 546 AF XY: 0.0530 AC XY: 7208 AN XY: 135898

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.0378

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.0739

Gnomad SAS exome AF: 0.0721

Gnomad FIN exome AF: 0.00633

Gnomad NFE exome AF: 0.0410

Gnomad OTH exome AF: 0.0629

GnomAD4 exome AF: 0.0462 AC: 67525 AN: 1461876 Hom.: 1987 Cov.: 32 AF XY: 0.0467 AC XY: 33990 AN XY: 727240

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0602

Gnomad4 SAS exome AF: 0.0733

Gnomad4 FIN exome AF: 0.00698

Gnomad4 NFE exome AF: 0.0402

Gnomad4 OTH exome AF: 0.0595

GnomAD4 genome AF: 0.0730 AC: 11109 AN: 152102 Hom.: 559 Cov.: 32 AF XY: 0.0704 AC XY: 5239 AN XY: 74366

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0755

Gnomad4 SAS AF: 0.0716

Gnomad4 FIN AF: 0.00519

Gnomad4 NFE AF: 0.0387

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0501 Hom.: 543

Bravo AF: 0.0803

TwinsUK AF: 0.0413 AC: 153

ALSPAC AF: 0.0472 AC: 182

ESP6500AA AF: 0.143 AC: 629

ESP6500EA AF: 0.0455 AC: 391

ExAC AF: 0.0547 AC: 6643

Asia WGS AF: 0.0760 AC: 262 AN: 3478

EpiCase AF: 0.0507

EpiControl AF: 0.0486

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.4
DANN	Benign	0.87
DEOGEN2	Benign	0.017	.;.;T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.67	T;T;T;T;T
MetaRNN	Benign	0.0015	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	.;N;N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.15	.;N;N;.;.
REVEL	Benign	0.035
Sift	Benign	0.27	.;T;T;.;.
Sift4G	Benign	0.69	.;T;T;T;T
Polyphen		0.0	.;B;B;.;.
Vest4		0.057, 0.038
MPC		0.39
ClinPred		0.0012	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.084

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

LitVar

Other links and lift over

dbSNP: rs2293507; hg19: chr7-70228020; COSMIC: COSV61421335; COSMIC: COSV61421335;