Variant 4-54048959-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012110.4(CHIC2):c.326A>G(p.Lys109Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 1,546,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CHIC2
NM_012110.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

Variant links:

Genes affected

CHIC2 (HGNC:1935): (cysteine rich hydrophobic domain 2) This gene encodes a member of the CHIC family of proteins. The encoded protein contains a cysteine-rich hydrophobic (CHIC) motif, and is localized to vesicular structures and the plasma membrane. This gene is associated with some cases of acute myeloid leukemia. [provided by RefSeq, Jul 2008]

CHIC2 links:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39078778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIC2	NM_012110.4 linkuse as main transcript	c.326A>G	p.Lys109Arg	missense_variant	3/6	ENST00000263921.8	NP_036242.1	Q9UKJ5
CHIC2	XM_011534382.3 linkuse as main transcript	c.326A>G	p.Lys109Arg	missense_variant	3/4		XP_011532684.1
CHIC2	XM_047450063.1 linkuse as main transcript	c.218A>G	p.Lys73Arg	missense_variant	4/7		XP_047306019.1
CHIC2	XM_006714037.5 linkuse as main transcript	c.246+80A>G		intron_variant			XP_006714100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIC2	ENST00000263921.8 linkuse as main transcript	c.326A>G	p.Lys109Arg	missense_variant	3/6	1	NM_012110.4	ENSP00000263921.3		Q9UKJ5
ENSG00000282278	ENST00000507166.5 linkuse as main transcript	c.1018-225966T>C		intron_variant		2		ENSP00000423325.1		A0A0B4J203

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000118

AC:

AN:

169218

Hom.:

AF XY:

0.0000111

AC XY:

AN XY:

90392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000645

AC:

AN:

1394386

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

688774

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:

0.00000834

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000838

AC:

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 31, 2023

The c.326A>G (p.K109R) alteration is located in exon 3 (coding exon 3) of the CHIC2 gene. This alteration results from a A to G substitution at nucleotide position 326, causing the lysine (K) at amino acid position 109 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.7

L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.16

Sift

Benign

0.27

T;T

Sift4G

Benign

0.22

T;T

Polyphen

1.0

D;.

Vest4

0.65

MutPred

0.48

Loss of methylation at K109 (P = 0.0116);Loss of methylation at K109 (P = 0.0116);

MVP

0.39

MPC

1.7

ClinPred

0.60

GERP RS

5.5

Varity_R

0.27

gMVP

0.54

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