rs2281627

chr9-116700910-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012210.4(TRIM32):c.*1206T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 166,942 control chromosomes in the GnomAD database, including 8,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7262 hom., cov: 33)
  • Exomes 𝑓: 0.38 (1069 hom.)
• Consequence: TRIM32 NM_012210.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.264

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-116700910-T-C is Benign according to our data. Variant chr9-116700910-T-C is described in ClinVar as [Benign]. Clinvar id is 364737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM32	NM_012210.4	c.*1206T>C		3_prime_UTR_variant	2/2	ENST00000450136.2
ASTN2	NM_001365068.1	c.2806+24861A>G		intron_variant		ENST00000313400.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM32	ENST00000450136.2	c.*1206T>C		3_prime_UTR_variant	2/2	1	NM_012210.4	P1
ASTN2	ENST00000313400.9	c.2806+24861A>G		intron_variant		5	NM_001365068.1	A2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43976 AN: 152028 Hom.: 7258 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.379 AC: 5608 AN: 14796 Hom.: 1069 Cov.: 0 AF XY: 0.379 AC XY: 2662 AN XY: 7026

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.289 AC: 43996 AN: 152146 Hom.: 7262 Cov.: 33 AF XY: 0.292 AC XY: 21703 AN XY: 74380

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.305

Alfa AF: 0.302 Hom.: 2351

Bravo AF: 0.291

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Sarcotubular myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Bardet-Biedl syndrome 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.5
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs2281627; hg19: chr9-119463189; COSMIC: COSV57773490; COSMIC: COSV57773490;