Variant 7-29194958-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004067.4(CHN2):c.17A>C(p.Asn6Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000785 in 1,582,974 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 1 hom. )

Consequence

CHN2
NM_004067.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Variant links:

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]

CHN2 links:

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

CPVL links:

Genome browser will be placed here

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=0.15196893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4 linkuse as main transcript	c.17A>C	p.Asn6Thr	missense_variant	1/13	ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11 linkuse as main transcript	c.17A>C	p.Asn6Thr	missense_variant	1/13	1	NM_004067.4	P1	P52757-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000292

AC:

AN:

212464

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

117504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000662

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000986

Gnomad NFE exome

AF:

0.000599

Gnomad OTH exome

AF:

0.000199

GnomAD4 exome

AF:

0.000845

AC:

1209

AN:

1430948

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

570

AN XY:

711662

show subpopulations

Gnomad4 AFR exome

AF:

0.0000329

Gnomad4 AMR exome

AF:

0.0000485

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.000137

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000217

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.000357

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 09, 2023

The c.17A>C (p.N6T) alteration is located in exon 1 (coding exon 1) of the CHN2 gene. This alteration results from a A to C substitution at nucleotide position 17, causing the asparagine (N) at amino acid position 6 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.043

T;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.72

T;T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Uncertain

-0.060

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

1.0

D;D;D;D;N;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.43

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.30

T;D;D

Sift4G

Benign

0.15

T;D;D

Polyphen

0.95

P;.;.

Vest4

0.24

MVP

0.85

MPC

0.99

ClinPred

0.27

GERP RS

4.1

Varity_R

0.31

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over