Variant 9-116697371-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBS1BS2

The NM_001379048.1(TRIM32):c.-142-2A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 289,224 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

TRIM32
NM_001379048.1 splice_acceptor, intron

Scores

Splicing: ADA: 0.3886

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.638

Variant links:

Genes affected

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:

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

BP6

Variant 9-116697371-A-G is Benign according to our data. Variant chr9-116697371-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1188514.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00816 (1243/152320) while in subpopulation AFR AF= 0.0289 (1202/41576). AF 95% confidence interval is 0.0276. There are 21 homozygotes in gnomad4. There are 582 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTN2	NM_001365068.1 link	c.2806+28400T>C		intron_variant		ENST00000313400.9	NP_001351997.1
TRIM32	NM_012210.4 link	c.-81-291A>G		intron_variant		ENST00000450136.2	NP_036342.2	Q13049A0A024R843

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTN2	ENST00000313400.9 link	c.2806+28400T>C		intron_variant		5	NM_001365068.1	ENSP00000314038.4		O75129-1
TRIM32	ENST00000450136.2 link	c.-81-291A>G		intron_variant		1	NM_012210.4	ENSP00000408292.1		Q13049

Frequencies

GnomAD3 genomes

AF:

0.00816

AC:

1242

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.00146

AC:

200

AN:

136904

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

72062

show subpopulations

Gnomad4 AFR exome

AF:

0.0365

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00816

AC:

1243

AN:

152320

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

582

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00931

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.8

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.39

dbscSNV1_RF

Pathogenic

0.73

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