chr9-116687330-G-C

Variant names:

• chr9-116687330-G-C
• rs12342207
• NM_012210.4:c.-133G>C

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 0.335
• Publications: 4 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRIM32	NM_012210.4	c.-133G>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000450136.2	NP_036342.2
ASTN2	NM_001365068.1	c.2807-35537C>G		intron_variant	Intron 16 of 22	ENST00000313400.9	NP_001351997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM32	ENST00000450136.2	c.-133G>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_012210.4	ENSP00000408292.1
ASTN2	ENST00000313400.9	c.2807-35537C>G		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4

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

African (AFR) AF: 0.100 AC: 1530 AN: 15252

American (AMR) AF: 0.420 AC: 500 AN: 1190

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 1321 AN: 5012

East Asian (EAS) AF: 0.317 AC: 1124 AN: 3542

South Asian (SAS) AF: 0.273 AC: 4368 AN: 16002

European-Finnish (FIN) AF: 0.326 AC: 94 AN: 288

Middle Eastern (MID) AF: 0.269 AC: 423 AN: 1570

European-Non Finnish (NFE) AF: 0.323 AC: 238712 AN: 737990

Other (OTH) AF: 0.312 AC: 8244 AN: 26396

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

African (AFR) AF: 0.116 AC: 4758 AN: 40978

American (AMR) AF: 0.416 AC: 6271 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 935 AN: 3454

East Asian (EAS) AF: 0.313 AC: 1552 AN: 4960

South Asian (SAS) AF: 0.257 AC: 1202 AN: 4678

European-Finnish (FIN) AF: 0.365 AC: 3766 AN: 10328

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21649 AN: 67476

Other (OTH) AF: 0.293 AC: 612 AN: 2090

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sarcotubular myopathy Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

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 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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

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 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	-0.81
CADD	Benign	9.4
DANN	Benign	0.50
PhyloP100		0.34
PromoterAI		0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12342207; hg19: chr9-119449609;