rs1661300

Positions:

chr9-116698996-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.427

Variant links:

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]

TRIM32 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 95495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-116698996-G-A is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM32	NM_012210.4 linkuse as main transcript	c.1254G>A	p.Val418Val	synonymous_variant	2/2	ENST00000450136.2	NP_036342.2	Q13049A0A024R843
ASTN2	NM_001365068.1 linkuse as main transcript	c.2806+26775C>T		intron_variant		ENST00000313400.9	NP_001351997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM32	ENST00000450136.2 linkuse as main transcript	c.1254G>A	p.Val418Val	synonymous_variant	2/2	1	NM_012210.4	ENSP00000408292.1		Q13049
ASTN2	ENST00000313400.9 linkuse as main transcript	c.2806+26775C>T		intron_variant		5	NM_001365068.1	ENSP00000314038.4		O75129-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16110

AN:

151972

Hom.:

925

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.111

AC:

27763

AN:

250520

Hom.:

1633

AF XY:

0.112

AC XY:

15113

AN XY:

135488

show subpopulations

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 SAS exome

AF:

0.0841

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.:

AF XY:

0.116

AC XY:

84304

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0687

Gnomad4 AMR exome

AF:

0.0823

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.0875

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.106

AC:

16124

AN:

152094

Hom.:

929

Cov.:

AF XY:

0.105

AC XY:

7812

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0719

Gnomad4 AMR

AF:

0.0865

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.0846

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.0930

Alfa

AF:

0.117

Hom.:

1779

Bravo

AF:

0.0996

Asia WGS

AF:

0.117

AC:

406

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.116

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 12, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Val418Val in exon 2 of TRIM32: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 12.7% (1093/8600) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1661300). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Sarcotubular myopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Bardet-Biedl syndrome 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.8

DANN

Benign

0.85

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over