7-29509310-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004067.4(CHN2):āc.1139A>Gā(p.Asn380Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000373 in 1,613,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00019 ( 0 hom., cov: 33)
Exomes š: 0.00039 ( 0 hom. )
Consequence
CHN2
NM_004067.4 missense
NM_004067.4 missense
Scores
2
11
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]
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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=0.110610574).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHN2 | NM_004067.4 | c.1139A>G | p.Asn380Ser | missense_variant | 12/13 | ENST00000222792.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHN2 | ENST00000222792.11 | c.1139A>G | p.Asn380Ser | missense_variant | 12/13 | 1 | NM_004067.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000227 AC: 57AN: 251400Hom.: 0 AF XY: 0.000228 AC XY: 31AN XY: 135876
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GnomAD4 exome AF: 0.000391 AC: 572AN: 1461182Hom.: 0 Cov.: 30 AF XY: 0.000400 AC XY: 291AN XY: 726940
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GnomAD4 genome AF: 0.000191 AC: 29AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74382
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2021 | The c.1139A>G (p.N380S) alteration is located in exon 12 (coding exon 12) of the CHN2 gene. This alteration results from a A to G substitution at nucleotide position 1139, causing the asparagine (N) at amino acid position 380 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
Polyphen
0.47, 0.0
.;P;.;.;B;B
Vest4
0.28, 0.25, 0.29, 0.31, 0.27
MVP
0.35
MPC
0.47
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at