rs1554489359

Variant names:

• chr7-70790776-C-G
• rs1554489359
• NM_015570.4:c.3560C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-70790776-C-G
• chr7-70790776-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015570.4(AUTS2):​c.3560C>G​(p.Pro1187Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P1187S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.3560C>G	p.Pro1187Arg	missense	Exon 19 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.3488C>G	p.Pro1163Arg	missense	Exon 18 of 18	NP_001120703.1	Q8WXX7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.3560C>G	p.Pro1187Arg	missense	Exon 19 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.3488C>G	p.Pro1163Arg	missense	Exon 18 of 18	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000644939.1		c.3557C>G	p.Pro1186Arg	missense	Exon 19 of 19	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.30		Gain of methylation at P1187 (P = 0.0158)
MVP		0.58
MPC		1.3
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.62
gMVP		0.51
Mutation Taster		=40/60	disease causing

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

Other links and lift over

dbSNP: rs1554489359; hg19: chr7-70255762;