Variant chr15-78602015-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000326828.6(CHRNA3):c.627C>G(p.Ile209Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,461,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I209I) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CHRNA3
ENST00000326828.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

CHRNA3 (HGNC:1957): (cholinergic receptor nicotinic alpha 3 subunit) This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

CHRNA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHRNA3	NM_000743.5 linkuse as main transcript	c.627C>G	p.Ile209Met	missense_variant	5/6	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2 linkuse as main transcript	c.627C>G	p.Ile209Met	missense_variant	5/6		NP_001160166.1
CHRNA3	XM_006720382.4 linkuse as main transcript	c.426C>G	p.Ile142Met	missense_variant	5/6		XP_006720445.1
CHRNA3	NR_046313.2 linkuse as main transcript	n.829C>G		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.627C>G	p.Ile209Met	missense_variant	5/6	1	NM_000743.5	ENSP00000315602	P1	P32297-2
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.627C>G	p.Ile209Met	missense_variant	5/6	1		ENSP00000267951		P32297-3
CHRNA3	ENST00000558903.1 linkuse as main transcript	n.334C>G		non_coding_transcript_exon_variant	2/2	4
CHRNA3	ENST00000559658.5 linkuse as main transcript	c.627C>G	p.Ile209Met	missense_variant, NMD_transcript_variant	5/8	2		ENSP00000452896		P32297-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251354

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135828

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461276

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000324

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

.;D

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.62

Sift

Benign

0.045

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

1.0

D;D

Vest4

0.86

MutPred

0.75

Gain of ubiquitination at K211 (P = 0.078);Gain of ubiquitination at K211 (P = 0.078);

MVP

0.85

MPC

0.89

ClinPred

0.91

GERP RS

4.3

Varity_R

0.62

gMVP

0.76

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over