rs12342207

Variant names:

• chr9-116687330-G-A
• rs12342207
• NM_012210.4:c.-133G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-116687330-G-A
• chr9-116687330-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012210.4(TRIM32):​c.-133G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 808,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 25)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: TRIM32 NM_012210.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM32	NM_012210.4	c.-133G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000450136.2	NP_036342.2
ASTN2	NM_001365068.1	c.2807-35537C>T		intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM32	ENST00000450136.2	c.-133G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_012210.4	ENSP00000408292.1
ASTN2	ENST00000313400.9	c.2807-35537C>T		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000124 AC: 1 AN: 808348 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 374078

African (AFR) AF: 0.00 AC: 0 AN: 15258

American (AMR) AF: 0.00 AC: 0 AN: 1192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5020

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 16020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1574

European-Non Finnish (NFE) AF: 0.00000135 AC: 1 AN: 739018

Other (OTH) AF: 0.00 AC: 0 AN: 26428

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.34
PromoterAI		0.091	Neutral

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

Other links and lift over

dbSNP: rs12342207; hg19: chr9-119449609;