9-116699696-ACC-GCA

Variant names:

• chr9-116699696-ACC-GCA
• NM_012210.4:c.1954_1956delACCinsGCA
• TRIM32 p.Thr652Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012210.4(TRIM32):​c.1954_1956delACCinsGCA​(p.Thr652Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T652I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM32 NM_012210.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.65
• Publications: 0 publications found

Genes affected

TRIM32 (HGNC:16380): (tripartite motif containing 32) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes. [provided by RefSeq, Jul 2008]

ASTN2 (HGNC:17021): (astrotactin 2) This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

ASTN2 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012210.4. 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
	TRIM32	NM_012210.4	MANE Select	c.1954_1956delACCinsGCA	p.Thr652Ala	missense	N/A	NP_036342.2	Q13049
	ASTN2	NM_001365068.1	MANE Select	c.2806+26073_2806+26075delGGTinsTGC		intron	N/A	NP_001351997.1	O75129-1
	TRIM32	NM_001099679.2		c.1954_1956delACCinsGCA	p.Thr652Ala	missense	N/A	NP_001093149.1	Q13049

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM32	ENST00000450136.2	TSL:1 MANE Select	c.1954_1956delACCinsGCA	p.Thr652Ala	missense	N/A	ENSP00000408292.1	Q13049
	TRIM32	ENST00000373983.2	TSL:1	c.1954_1956delACCinsGCA	p.Thr652Ala	missense	N/A	ENSP00000363095.1	Q13049
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.2806+26073_2806+26075delGGTinsTGC		intron	N/A	ENSP00000314038.4	O75129-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-119461975;