chr9-116699833-C-T

Variant names:

• chr9-116699833-C-T
• rs3019
• NM_012210.4:c.*129C>T

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.*129C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 1,250,184 control chromosomes in the GnomAD database, including 532,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67178 hom., cov: 32)
  • Exomes 𝑓: 0.92 (465375 hom.)
• Consequence: TRIM32 NM_012210.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.764
• Publications: 15 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=-0.63).
• BP6: Variant 9-116699833-C-T is Benign according to our data. Variant chr9-116699833-C-T is described in ClinVar as Benign. ClinVar VariationId is 364723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 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.*129C>T		3_prime_UTR	Exon 2 of 2	NP_036342.2	Q13049
	ASTN2	NM_001365068.1	MANE Select	c.2806+25938G>A		intron	N/A	NP_001351997.1	O75129-1
	TRIM32	NM_001099679.2		c.*129C>T		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.*129C>T		3_prime_UTR	Exon 2 of 2	ENSP00000408292.1	Q13049
	TRIM32	ENST00000373983.2	TSL:1	c.*129C>T		3_prime_UTR	Exon 2 of 2	ENSP00000363095.1	Q13049
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.2806+25938G>A		intron	N/A	ENSP00000314038.4	O75129-1

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142862 AN: 152184 Hom.: 67123 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.938

GnomAD4 exome AF: 0.920 AC: 1010442 AN: 1097882 Hom.: 465375 Cov.: 14 AF XY: 0.921 AC XY: 510048 AN XY: 553862

African (AFR) AF: 0.979 AC: 24167 AN: 24684

American (AMR) AF: 0.940 AC: 27348 AN: 29084

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 19914 AN: 21212

East Asian (EAS) AF: 0.970 AC: 34574 AN: 35638

South Asian (SAS) AF: 0.935 AC: 64436 AN: 68938

European-Finnish (FIN) AF: 0.963 AC: 47330 AN: 49156

Middle Eastern (MID) AF: 0.964 AC: 4284 AN: 4442

European-Non Finnish (NFE) AF: 0.911 AC: 744149 AN: 816860

Other (OTH) AF: 0.924 AC: 44240 AN: 47868

GnomAD4 genome AF: 0.939 AC: 142975 AN: 152302 Hom.: 67178 Cov.: 32 AF XY: 0.941 AC XY: 70059 AN XY: 74460

African (AFR) AF: 0.976 AC: 40562 AN: 41564

American (AMR) AF: 0.923 AC: 14122 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3268 AN: 3472

East Asian (EAS) AF: 0.970 AC: 5023 AN: 5180

South Asian (SAS) AF: 0.931 AC: 4489 AN: 4820

European-Finnish (FIN) AF: 0.967 AC: 10272 AN: 10622

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62139 AN: 68030

Other (OTH) AF: 0.935 AC: 1968 AN: 2104

Alfa AF: 0.923 Hom.: 89134

Bravo AF: 0.938

Asia WGS AF: 0.943 AC: 3276 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome 11 (1)
-	-	1	Sarcotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.6
DANN	Benign	0.47
PhyloP100		0.76
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: rs3019; hg19: chr9-119462112;