9-116698965-G-C

Variant names:

• chr9-116698965-G-C
• rs183136193
• NM_012210.4:c.1223G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012210.4(TRIM32):​c.1223G>C​(p.Arg408Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM32 NM_012210.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM32	NM_012210.4	c.1223G>C	p.Arg408Pro	missense_variant	Exon 2 of 2	ENST00000450136.2	NP_036342.2
ASTN2	NM_001365068.1	c.2806+26806C>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.1223G>C	p.Arg408Pro	missense_variant	Exon 2 of 2	1	NM_012210.4	ENSP00000408292.1
ASTN2	ENST00000313400.9	c.2806+26806C>G		intron_variant	Intron 16 of 22	5	NM_001365068.1	ENSP00000314038.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	0.076
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.62	N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0080	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.072	B;B
Vest4		0.86
MutPred		0.44		Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);
MVP		0.97
MPC		0.97
ClinPred		0.74	D
GERP RS		5.5
Varity_R		0.46
gMVP		0.93

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: rs183136193; hg19: chr9-119461244;