9-116698554-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012210.4(TRIM32):​c.812G>C​(p.Arg271Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R271G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TRIM32
NM_012210.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16724855).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM32NM_012210.4 linkc.812G>C p.Arg271Pro missense_variant Exon 2 of 2 ENST00000450136.2 NP_036342.2 Q13049A0A024R843
ASTN2NM_001365068.1 linkc.2806+27217C>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
TRIM32ENST00000450136.2 linkc.812G>C p.Arg271Pro missense_variant Exon 2 of 2 1 NM_012210.4 ENSP00000408292.1 Q13049
ASTN2ENST00000313400.9 linkc.2806+27217C>G intron_variant Intron 16 of 22 5 NM_001365068.1 ENSP00000314038.4 O75129-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461642
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.020
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
19
DANN
Benign
0.93
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.10
Eigen_PC
Benign
0.087
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.82
T;.
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.96
N;N
REVEL
Benign
0.17
Sift
Benign
0.36
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.23
B;B
Vest4
0.31
MutPred
0.46
Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);
MVP
0.95
MPC
0.35
ClinPred
0.18
T
GERP RS
4.3
Varity_R
0.15
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-119460833; API