9-116687339-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_012210.4(TRIM32):c.-124G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 909,894 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

TRIM32
NM_012210.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.89

Publications

1 publications found

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 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

ASTN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000397 (60/151206) while in subpopulation NFE AF = 0.000811 (55/67808). AF 95% confidence interval is 0.00064. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRIM32	NM_012210.4 link	c.-124G>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000450136.2	NP_036342.2	Q13049A0A024R843
TRIM32	NM_012210.4 link	c.-124G>A	5_prime_UTR_variant	Exon 1 of 2	ENST00000450136.2	NP_036342.2	Q13049A0A024R843
ASTN2	NM_001365068.1 link	c.2807-35546C>T	intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM32	ENST00000450136.2 link	c.-124G>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_012210.4	ENSP00000408292.1	Q13049
TRIM32	ENST00000450136.2 link	c.-124G>A	5_prime_UTR_variant	Exon 1 of 2	1	NM_012210.4	ENSP00000408292.1	Q13049
ASTN2	ENST00000313400.9 link	c.2807-35546C>T	intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4	O75129-1

Frequencies

GnomAD3 genomes

AF:

0.000397

AC:

AN:

151206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000811

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00123

AC:

932

AN:

758688

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

424

AN XY:

351598

show subpopulations

African (AFR)

AF:

0.000141

AC:

AN:

14226

American (AMR)

AF:

0.00

AC:

AN:

1158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4718

East Asian (EAS)

AF:

0.00

AC:

AN:

3288

South Asian (SAS)

AF:

0.00

AC:

AN:

15036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1488

European-Non Finnish (NFE)

AF:

0.00128

AC:

885

AN:

693696

Other (OTH)

AF:

0.00181

AC:

AN:

24820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000397

AC:

AN:

151206

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

73832

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

41086

American (AMR)

AF:

0.00

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000811

AC:

AN:

67808

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000693

Hom.:

Bravo

AF:

0.000408

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Sarcotubular myopathy

Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Bardet-Biedl syndrome 11

Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.9

PromoterAI

0.29

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-116687339-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over