7-69599742-T-G

Position:

• chr7-69599742-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015570.4(AUTS2):​c.89T>G​(p.Leu30Arg) variant causes a missense change involving the alteration of a non-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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.993

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20940802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.89T>G	p.Leu30Arg	missense_variant	1/19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.89T>G	p.Leu30Arg	missense_variant	1/19	1	NM_015570.4	ENSP00000344087	P4
AUTS2	ENST00000406775.6	c.89T>G	p.Leu30Arg	missense_variant	1/18	1		ENSP00000385263
AUTS2	ENST00000403018.3	c.89T>G	p.Leu30Arg	missense_variant	1/5	1		ENSP00000385572
AUTS2	ENST00000644939.1	c.89T>G	p.Leu30Arg	missense_variant	1/19			ENSP00000496726	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 03, 2023

The c.89T>G (p.L30R) alteration is located in exon 1 (coding exon 1) of the AUTS2 gene. This alteration results from a T to G substitution at nucleotide position 89, causing the leucine (L) at amino acid position 30 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.50	T;T;T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N;N;N
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	0.39	.;N;N;N
REVEL	Benign	0.062
Sift	Pathogenic	0.0	.;D;D;T
Sift4G	Benign	0.21	.;T;T;T
Polyphen		0.83	.;P;P;.
Vest4		0.10, 0.088, 0.063
MutPred		0.36		Gain of methylation at L30 (P = 6e-04);Gain of methylation at L30 (P = 6e-04);Gain of methylation at L30 (P = 6e-04);Gain of methylation at L30 (P = 6e-04);
MVP		0.068
MPC		3.3
ClinPred		0.61	D
GERP RS		3.7
Varity_R		0.33
gMVP		0.050

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: chr7-69064728;