7-69599223-A-T

Variant names:

• chr7-69599223-A-T
• rs968543349
• NM_015570.4:c.-431A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015570.4(AUTS2):​c.-431A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: AUTS2 NM_015570.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991
• Publications: 0 publications found

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]

AUTS2 Gene-Disease associations (from GenCC):

• autism spectrum disorder due to AUTS2 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.-431A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_015570.4	MANE Select	c.-431A>T		5_prime_UTR	Exon 1 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.-431A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001120703.1	Q8WXX7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.-431A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.-431A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.-431A>T		5_prime_UTR	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1

Frequencies

GnomAD3 genomes AF: 0.0000142 AC: 2 AN: 140816 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000142 AC: 2 AN: 140954 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 68388

African (AFR) AF: 0.0000507 AC: 2 AN: 39434

American (AMR) AF: 0.00 AC: 0 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3310

East Asian (EAS) AF: 0.00 AC: 0 AN: 3944

South Asian (SAS) AF: 0.00 AC: 0 AN: 3768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64210

Other (OTH) AF: 0.00 AC: 0 AN: 2002

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		0.99
PromoterAI		-0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs968543349; hg19: chr7-69064209;