CHRNE p.Gly13Arg

Variant names:

• chr17-4903027-C-G
• NM_000080.4:c.37G>C
• CHRNE p.Gly13Arg

Your query was ambiguous. Multiple possible variants found:

• chr17-4903027-C-G
• chr17-4903027-C-T
• chr17-4903025-CCC-ACG
• chr17-4903025-CCC-GCG
• chr17-4903025-CCC-TCG
• chr17-4903025-CCC-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1_Moderate PM2

The NM_000080.4(CHRNE):​c.37G>C​(p.Gly13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G13G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRNE NM_000080.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 0 publications found

Genes affected

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

C17orf107 (HGNC:37238): (chromosome 17 open reading frame 107)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_000080.4 (CHRNE) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	NM_000080.4	MANE Select	c.37G>C	p.Gly13Arg	missense	Exon 1 of 12	NP_000071.1	Q04844
	C17orf107	NM_001145536.2	MANE Select	c.*2494C>G		downstream_gene	N/A	NP_001139008.1	Q6ZR85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	ENST00000649488.2	MANE Select	c.37G>C	p.Gly13Arg	missense	Exon 1 of 12	ENSP00000497829.1	Q04844
	CHRNE	ENST00000649830.1		c.-887-264G>C		intron	N/A	ENSP00000496907.1	A0A3B3IRM1
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*2494C>G		downstream_gene	N/A	ENSP00000370770.3	Q6ZR85

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.047
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.46
Sift	Benign	0.53	T
Sift4G	Benign	0.31	T
PromoterAI		-0.050	Neutral
Varity_R		0.066
gMVP		0.63

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-4806322;