rs200189077

Variant names:

• chr7-69599664-C-G
• NM_015570.4:c.11C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-69599664-C-G
• chr7-69599664-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015570.4(AUTS2):​c.11C>G​(p.Pro4Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000406775.6	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 18	1		ENSP00000385263.2
AUTS2	ENST00000403018.3	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 5	1		ENSP00000385572.2
AUTS2	ENST00000644939.1	c.11C>G	p.Pro4Arg	missense_variant	Exon 1 of 19			ENSP00000496726.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	.;.;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.1	.;L;L;L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.66	.;N;N;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Uncertain	0.013	.;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.47, 0.46, 0.54
MutPred		0.45		Gain of methylation at P4 (P = 0.005);Gain of methylation at P4 (P = 0.005);Gain of methylation at P4 (P = 0.005);Gain of methylation at P4 (P = 0.005);
MVP		0.41
MPC		2.8
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.32
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-69064650;