rs1010559927

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001346127.1(CHAC2):c.-113C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CHAC2
NM_001346127.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

Publications

1 publications found

Variant links:

Genes affected

CHAC2 (HGNC:32363): (ChaC glutathione specific gamma-glutamylcyclotransferase 2) The protein encoded by this gene is a gamma-glutamyl cyclotransferase that catalyzes the conversion of glutathione to 5-oxoproline and cysteinylglycine. It is thought that this gene is upregulated in response to endoplasmic reticulum stress and that the glutathione depletion enhances apoptosis. [provided by RefSeq, Sep 2016]

CHAC2 links:

ASB3 (HGNC:16013): (ankyrin repeat and SOCS box containing 3) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2011]

ASB3 links:

GPR75-ASB3 (HGNC:40043): (GPR75-ASB3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring GPR75 (G protein-coupled receptor 75) and ASB3 (ankyrin repeat and SOCS box containing 3) on chromosome 2. The transcript includes exons from both GPR75 and ASB3 and translation initiates in the 5' non-coding exon of GPR75. The resulting protein has a novel N-terminus but is otherwise identical to that encoded by ASB3.[provided by RefSeq, Feb 2011]

GPR75-ASB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346127.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHAC2	NM_001008708.4	MANE Select	c.61C>A	p.Leu21Met	missense	Exon 1 of 3	NP_001008708.1	Q8WUX2
ASB3	NM_016115.5	MANE Select	c.-13-2362G>T		intron	N/A	NP_057199.1	Q9Y575-1
CHAC2	NM_001346127.1		c.-113C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001333056.1	Q8WUX2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHAC2	ENST00000295304.5	TSL:1 MANE Select	c.61C>A	p.Leu21Met	missense	Exon 1 of 3	ENSP00000295304.4	Q8WUX2
ASB3	ENST00000263634.8	TSL:1 MANE Select	c.-13-2362G>T		intron	N/A	ENSP00000263634.2	Q9Y575-1
CHAC2	ENST00000893858.1		c.61C>A	p.Leu21Met	missense	Exon 1 of 2	ENSP00000563917.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.70

M_CAP

Benign

0.0054

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.27

PhyloP100

0.20

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.13

REVEL

Benign

0.063

Sift

Benign

0.26

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.15

MutPred

0.55

Loss of methylation at K20 (P = 0.0325)

MVP

0.19

MPC

0.0025

ClinPred

0.087

GERP RS

2.5

PromoterAI

0.25

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.31

gMVP

0.40

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -14

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over