7-69599742-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_015570(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 Genomes 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 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.993

Links

AUTS2 (HGNC:14262):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, Median coverage is 32.

BP4

Computational evidence support a benign effect (MetaRNN=0.20940802).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10 linkuse as main transcript	c.89T>G	p.Leu30Arg	missense_variant	1/19	1	NM_015570.4	P4	Q8WXX7-1
AUTS2	ENST00000406775.6 linkuse as main transcript	c.89T>G	p.Leu30Arg	missense_variant	1/18	1			Q8WXX7-2
AUTS2	ENST00000403018.3 linkuse as main transcript	c.89T>G	p.Leu30Arg	missense_variant	1/5	1			Q8WXX7-3
AUTS2	ENST00000644939.1 linkuse as main transcript	c.89T>G	p.Leu30Arg	missense_variant	1/19			A1

Frequencies

GnomAD3 genomes

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.50

T;T;T;T

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.93

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

GERP RS

3.7

Varity_R

0.33

gMVP

0.050

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over