chr15-78596693-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000743.5(CHRNA3):c.1429C>A(p.Arg477Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R477H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000743.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA3 | NM_000743.5 | c.1429C>A | p.Arg477Ser | missense_variant | 6/6 | ENST00000326828.6 | |
CHRNA3 | XM_006720382.4 | c.1228C>A | p.Arg410Ser | missense_variant | 6/6 | ||
CHRNA3 | NM_001166694.2 | c.1390-3502C>A | intron_variant | ||||
CHRNA3 | NR_046313.2 | n.1631C>A | non_coding_transcript_exon_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA3 | ENST00000326828.6 | c.1429C>A | p.Arg477Ser | missense_variant | 6/6 | 1 | NM_000743.5 | P1 | |
CHRNA3 | ENST00000348639.7 | c.1390-3502C>A | intron_variant | 1 | |||||
CHRNA3 | ENST00000559002.5 | n.40C>A | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
CHRNA3 | ENST00000559658.5 | c.1429C>A | p.Arg477Ser | missense_variant, NMD_transcript_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134798
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460464Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726578
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2022 | The c.1429C>A (p.R477S) alteration is located in exon 6 (coding exon 6) of the CHRNA3 gene. This alteration results from a C to A substitution at nucleotide position 1429, causing the arginine (R) at amino acid position 477 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at