chr7-69599679-G-C

Position:

• chr7-69599679-G-C

Variant summary

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

The NM_015570.4(AUTS2):​c.26G>C​(p.Gly9Ala) variant causes a missense change involving the alteration of a 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AUTS2 NM_015570.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

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=0.3942241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.26G>C	p.Gly9Ala	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.26G>C	p.Gly9Ala	missense_variant	1/19	1	NM_015570.4	ENSP00000344087.4
AUTS2	ENST00000406775.6	c.26G>C	p.Gly9Ala	missense_variant	1/18	1		ENSP00000385263.2
AUTS2	ENST00000403018.3	c.26G>C	p.Gly9Ala	missense_variant	1/5	1		ENSP00000385572.2
AUTS2	ENST00000644939.1	c.26G>C	p.Gly9Ala	missense_variant	1/19			ENSP00000496726.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1174524 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 567956

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: 0.00

Gnomad4 OTH exome AF: 0.00

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	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;.;T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	.;L;L;L
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.51	.;N;N;N
REVEL	Benign	0.094
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Uncertain	0.045	.;D;D;D
Polyphen		0.30	.;B;B;.
Vest4		0.28, 0.30, 0.33
MutPred		0.28		Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP		0.42
MPC		2.8
ClinPred		0.96	D
GERP RS		3.6
Varity_R		0.30
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs1792260195; hg19: chr7-69064665;