7-69599669-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM2_SupportingBP4

The NM_015570(AUTS2):c.16C>T(p.Arg6Trp) 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: 1.40

Links

AUTS2 (HGNC:14262):

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance.

PM2

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

BP4

Computational evidence support a benign effect (MetaRNN=0.39441597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4 linkuse as main transcript	c.16C>T	p.Arg6Trp	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.16C>T	p.Arg6Trp	missense_variant	1/19	1	NM_015570.4	P4	Q8WXX7-1
AUTS2	ENST00000406775.6 linkuse as main transcript	c.16C>T	p.Arg6Trp	missense_variant	1/18	1			Q8WXX7-2
AUTS2	ENST00000403018.3 linkuse as main transcript	c.16C>T	p.Arg6Trp	missense_variant	1/5	1			Q8WXX7-3
AUTS2	ENST00000644939.1 linkuse as main transcript	c.16C>T	p.Arg6Trp	missense_variant	1/19			A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000311

AC:

AN:

321472

Hom.:

AF XY:

0.00000584

AC XY:

AN XY:

171202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000496

Gnomad4 OTH exome

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 11, 2023

The c.16C>T (p.R6W) alteration is located in exon 1 (coding exon 1) of the AUTS2 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the arginine (R) at amino acid position 6 to be replaced by a tryptophan (W). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.17

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Pathogenic

0.94

Polyphen

0.89

.;P;P;.

Vest4

0.25, 0.21, 0.28

MutPred

0.33

Loss of methylation at R6 (P = 0.0069);Loss of methylation at R6 (P = 0.0069);Loss of methylation at R6 (P = 0.0069);Loss of methylation at R6 (P = 0.0069);

MVP

0.23

MPC

2.6

ClinPred

0.85

GERP RS

3.7

Varity_R

0.25

gMVP

0.13

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over