rs1661300

Variant names:

• chr9-116698996-G-A
• rs1661300
• NM_012210.4:c.1254G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012210.4(TRIM32):​c.1254G>A​(p.Val418Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,940 control chromosomes in the GnomAD database, including 11,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (929 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10123 hom.)
• Consequence: TRIM32 NM_012210.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.427
• Publications: 17 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 9-116698996-G-A is Benign according to our data. Variant chr9-116698996-G-A is described in ClinVar as Benign. ClinVar VariationId is 95495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.427 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 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.1254G>A	p.Val418Val	synonymous	Exon 2 of 2	NP_036342.2	Q13049
	ASTN2	NM_001365068.1	MANE Select	c.2806+26775C>T		intron	N/A	NP_001351997.1	O75129-1
	TRIM32	NM_001099679.2		c.1254G>A	p.Val418Val	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.1254G>A	p.Val418Val	synonymous	Exon 2 of 2	ENSP00000408292.1	Q13049
	TRIM32	ENST00000373983.2	TSL:1	c.1254G>A	p.Val418Val	synonymous	Exon 2 of 2	ENSP00000363095.1	Q13049
	ASTN2	ENST00000313400.9	TSL:5 MANE Select	c.2806+26775C>T		intron	N/A	ENSP00000314038.4	O75129-1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16110 AN: 151972 Hom.: 925 Cov.: 33

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0936

GnomAD2 exomes AF: 0.111 AC: 27763 AN: 250520 AF XY: 0.112

Gnomad AFR exome AF: 0.0696

Gnomad AMR exome AF: 0.0809

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.116 AC: 169788 AN: 1461846 Hom.: 10123 Cov.: 32 AF XY: 0.116 AC XY: 84304 AN XY: 727222

African (AFR) AF: 0.0687 AC: 2299 AN: 33480

American (AMR) AF: 0.0823 AC: 3680 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 4009 AN: 26136

East Asian (EAS) AF: 0.139 AC: 5531 AN: 39700

South Asian (SAS) AF: 0.0875 AC: 7546 AN: 86256

European-Finnish (FIN) AF: 0.134 AC: 7163 AN: 53374

Middle Eastern (MID) AF: 0.0981 AC: 566 AN: 5768

European-Non Finnish (NFE) AF: 0.119 AC: 131861 AN: 1112012

Other (OTH) AF: 0.118 AC: 7133 AN: 60396

GnomAD4 genome AF: 0.106 AC: 16124 AN: 152094 Hom.: 929 Cov.: 33 AF XY: 0.105 AC XY: 7812 AN XY: 74336

African (AFR) AF: 0.0719 AC: 2985 AN: 41500

American (AMR) AF: 0.0865 AC: 1323 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.149 AC: 768 AN: 5148

South Asian (SAS) AF: 0.0846 AC: 407 AN: 4812

European-Finnish (FIN) AF: 0.140 AC: 1487 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8333 AN: 67970

Other (OTH) AF: 0.0930 AC: 196 AN: 2108

Alfa AF: 0.116 Hom.: 2535

Bravo AF: 0.0996

Asia WGS AF: 0.117 AC: 406 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.116

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Sarcotubular myopathy (2)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.8
DANN	Benign	0.85
PhyloP100		0.43
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: rs1661300; hg19: chr9-119461275; COSMIC: COSV57778458; COSMIC: COSV57778458;