dbSNP rs267606725: CHRNG:p.Gln5Lys (chr2-232539760-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005199.5(CHRNG):c.13C>A(p.Gln5Lys) 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 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHRNG
NM_005199.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.259

Publications

0 publications found

Variant links:

Genes affected

CHRNG (HGNC:1967): (cholinergic receptor nicotinic gamma subunit) The mammalian muscle-type acetylcholine receptor is a transmembrane pentameric glycoprotein with two alpha subunits, one beta, one delta, and one epsilon (in adult skeletal muscle) or gamma (in fetal and denervated muscle) subunit. This gene, which encodes the gamma subunit, is expressed prior to the thirty-third week of gestation in humans. The gamma subunit of the acetylcholine receptor plays a role in neuromuscular organogenesis and ligand binding and disruption of gamma subunit expression prevents the correct localization of the receptor in cell membranes. Mutations in this gene cause Escobar syndrome and a lethal form of multiple pterygium syndrome. Muscle-type acetylcholine receptor is the major antigen in the autoimmune disease myasthenia gravis.[provided by RefSeq, Sep 2009]

CHRNG Gene-Disease associations (from GenCC):

autosomal recessive multiple pterygium syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet
CHRNG-associated hypo-akinesia disorder of prenatal onset
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
lethal multiple pterygium syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet
transient neonatal myasthenia gravis
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

CHRNG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13715309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNG	NM_005199.5 link	c.13C>A	p.Gln5Lys	missense_variant	Exon 1 of 12	ENST00000651502.1	NP_005190.4	P07510-1A0A6F7YAP6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNG	ENST00000651502.1 link	c.13C>A	p.Gln5Lys	missense_variant	Exon 1 of 12		NM_005199.5	ENSP00000498757.1	P07510-1
CHRNG	ENST00000389492.3 link	c.13C>A	p.Gln5Lys	missense_variant	Exon 1 of 11	1		ENSP00000374143.3	P07510-2
CHRNG	ENST00000485094.1 link	n.34C>A		non_coding_transcript_exon_variant	Exon 1 of 5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.6

L;L

PhyloP100

0.26

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.24

Sift

Benign

0.34

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.71

P;.

Vest4

0.30

MutPred

0.42

Gain of glycosylation at Q5 (P = 0.016);Gain of glycosylation at Q5 (P = 0.016);

MVP

0.60

MPC

0.18

ClinPred

0.20

GERP RS

1.7

PromoterAI

-0.0096

Neutral

(source)

Varity_R

0.14

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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.

rs267606725

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over