rs751042207
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000743.5(CHRNA3):c.1429C>T(p.Arg477Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,438 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.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CHRNA3
NM_000743.5 missense
NM_000743.5 missense
Scores
16
2
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.17
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.971
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA3 | NM_000743.5 | c.1429C>T | p.Arg477Cys | missense_variant | Exon 6 of 6 | ENST00000326828.6 | NP_000734.2 | |
CHRNA3 | XM_006720382.4 | c.1228C>T | p.Arg410Cys | missense_variant | Exon 6 of 6 | XP_006720445.1 | ||
CHRNA3 | NM_001166694.2 | c.1390-3502C>T | intron_variant | Intron 5 of 5 | NP_001160166.1 | |||
CHRNA3 | NR_046313.2 | n.1631C>T | non_coding_transcript_exon_variant | Exon 6 of 8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNA3 | ENST00000326828.6 | c.1429C>T | p.Arg477Cys | missense_variant | Exon 6 of 6 | 1 | NM_000743.5 | ENSP00000315602.5 | ||
CHRNA3 | ENST00000348639.7 | c.1390-3502C>T | intron_variant | Intron 5 of 5 | 1 | ENSP00000267951.4 | ||||
CHRNA3 | ENST00000559002.5 | n.40C>T | non_coding_transcript_exon_variant | Exon 1 of 2 | 1 | |||||
CHRNA3 | ENST00000559658.5 | n.1429C>T | non_coding_transcript_exon_variant | Exon 6 of 8 | 2 | ENSP00000452896.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249190Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134798
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460466Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726580
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74230
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0609);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at