NM_012210.4:c.*1206T>C

Variant names:

• chr9-116700910-T-C
• rs2281627
• NM_012210.4:c.*1206T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012210.4(TRIM32):​c.*1206T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 166,942 control chromosomes in the GnomAD database, including 8,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7262 hom., cov: 33)
  • Exomes 𝑓: 0.38 (1069 hom.)
• Consequence: TRIM32 NM_012210.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.264
• Publications: 8 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-116700910-T-C is Benign according to our data. Variant chr9-116700910-T-C is described in ClinVar as Benign. ClinVar VariationId is 364737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

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.*1206T>C		3_prime_UTR	Exon 2 of 2	NP_036342.2	Q13049
	ASTN2	NM_001365068.1	MANE Select	c.2806+24861A>G		intron	N/A	NP_001351997.1	O75129-1
	TRIM32	NM_001099679.2		c.*1206T>C		3_prime_UTR	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.*1206T>C		3_prime_UTR	Exon 2 of 2	ENSP00000408292.1	Q13049
	TRIM32	ENST00000373983.2	TSL:1	c.*1206T>C		3_prime_UTR	Exon 2 of 2	ENSP00000363095.1	Q13049
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.2806+24861A>G		intron	N/A	ENSP00000314038.4	O75129-1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43976 AN: 152028 Hom.: 7258 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.379 AC: 5608 AN: 14796 Hom.: 1069 Cov.: 0 AF XY: 0.379 AC XY: 2662 AN XY: 7026

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.379 AC: 5533 AN: 14608

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.405 AC: 34 AN: 84

Other (OTH) AF: 0.378 AC: 34 AN: 90

GnomAD4 genome AF: 0.289 AC: 43996 AN: 152146 Hom.: 7262 Cov.: 33 AF XY: 0.292 AC XY: 21703 AN XY: 74380

African (AFR) AF: 0.138 AC: 5725 AN: 41530

American (AMR) AF: 0.425 AC: 6487 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1661 AN: 5172

South Asian (SAS) AF: 0.262 AC: 1264 AN: 4822

European-Finnish (FIN) AF: 0.373 AC: 3949 AN: 10592

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22881 AN: 67968

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.305 Hom.: 3529

Bravo AF: 0.291

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome 11 (1)
-	-	1	not provided (1)
-	-	1	Sarcotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs2281627; hg19: chr9-119463189; COSMIC: COSV57773490; COSMIC: COSV57773490;