7-69599744-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015570.4(AUTS2):c.91G>A(p.Gly31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000833 in 1,199,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. G31V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27537096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.91G>A	p.Gly31Arg	missense_variant	1/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.91G>A	p.Gly31Arg	missense_variant	1/19	1	NM_015570.4	P4
AUTS2	ENST00000406775.6	c.91G>A	p.Gly31Arg	missense_variant	1/18	1
AUTS2	ENST00000403018.3	c.91G>A	p.Gly31Arg	missense_variant	1/5	1
AUTS2	ENST00000644939.1	c.91G>A	p.Gly31Arg	missense_variant	1/19			A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.33e-7 AC: 1 AN: 1199976 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 583256

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: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

Autism spectrum disorder due to AUTS2 deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.12

T

BayesDel_noAF

Benign

-0.41

Cadd

Uncertain

25

Dann

Uncertain

1.0

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.74

D

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Uncertain

0.15

D

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.93

T

MutationTaster

Benign

0.65

N;N;N

PrimateAI

Pathogenic

0.94

D

Polyphen

0.93

.;P;P;.

Vest4

0.12, 0.11, 0.10

MutPred

0.20

Gain of methylation at G31 (P = 0.0033);Gain of methylation at G31 (P = 0.0033);Gain of methylation at G31 (P = 0.0033);Gain of methylation at G31 (P = 0.0033);

MVP

0.13

MPC

3.1

ClinPred

0.70

D

GERP RS

3.7

Varity_R

0.11

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: chr7-69064730;