NM_012210.4:c.693A>G

Variant names:

• chr9-116698435-A-G
• NM_012210.4:c.693A>G
• TRIM32 p.Ala231Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012210.4(TRIM32):​c.693A>G​(p.Ala231Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A231A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM32 NM_012210.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.

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.693A>G	p.Ala231Ala	synonymous	Exon 2 of 2	NP_036342.2	Q13049
	ASTN2	NM_001365068.1	MANE Select	c.2806+27336T>C		intron	N/A	NP_001351997.1	O75129-1
	TRIM32	NM_001099679.2		c.693A>G	p.Ala231Ala	synonymous	Exon 2 of 2	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.693A>G	p.Ala231Ala	synonymous	Exon 2 of 2	ENSP00000408292.1	Q13049
	TRIM32	ENST00000373983.2	TSL:1	c.693A>G	p.Ala231Ala	synonymous	Exon 2 of 2	ENSP00000363095.1	Q13049
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.2806+27336T>C		intron	N/A	ENSP00000314038.4	O75129-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.61
PhyloP100		-1.8

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

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

Other links and lift over

hg19: chr9-119460714;