chr9-116687330-G-C

Position:

• chr9-116687330-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012210.4(TRIM32):​c.-133G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 957,472 control chromosomes in the GnomAD database, including 48,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6618 hom., cov: 25)
  • Exomes 𝑓: 0.32 (41425 hom.)
• Consequence: TRIM32 NM_012210.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.335

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-116687330-G-C is Benign according to our data. Variant chr9-116687330-G-C is described in ClinVar as [Benign]. Clinvar id is 364712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM32	NM_012210.4	c.-133G>C		5_prime_UTR_variant	1/2	ENST00000450136.2
ASTN2	NM_001365068.1	c.2807-35537C>G		intron_variant		ENST00000313400.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM32	ENST00000450136.2	c.-133G>C		5_prime_UTR_variant	1/2	1	NM_012210.4	P1
ASTN2	ENST00000313400.9	c.2807-35537C>G		intron_variant		5	NM_001365068.1	A2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41142 AN: 150118 Hom.: 6616 Cov.: 25

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.318 AC: 256316 AN: 807242 Hom.: 41425 Cov.: 13 AF XY: 0.319 AC XY: 118999 AN XY: 373606

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.274 AC: 41156 AN: 150230 Hom.: 6618 Cov.: 25 AF XY: 0.277 AC XY: 20284 AN XY: 73240

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.293

Alfa AF: 0.294 Hom.: 894

Bravo AF: 0.277

Asia WGS AF: 0.293 AC: 1017 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Sarcotubular myopathy 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. -

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

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.50

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: rs12342207; hg19: chr9-119449609;