8-42756210-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_004198.3(CHRNA6):c.989G>A(p.Arg330His) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,614,006 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 (★).
Frequency
Consequence
NM_004198.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA6 | NM_004198.3 | c.989G>A | p.Arg330His | missense_variant | Exon 5 of 6 | ENST00000276410.7 | NP_004189.1 | |
CHRNA6 | NM_001199279.1 | c.944G>A | p.Arg315His | missense_variant | Exon 4 of 5 | NP_001186208.1 | ||
CHRNA6 | XM_047422396.1 | c.989G>A | p.Arg330His | missense_variant | Exon 6 of 7 | XP_047278352.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNA6 | ENST00000276410.7 | c.989G>A | p.Arg330His | missense_variant | Exon 5 of 6 | 1 | NM_004198.3 | ENSP00000276410.3 | ||
CHRNA6 | ENST00000534622.5 | c.944G>A | p.Arg315His | missense_variant | Exon 4 of 5 | 2 | ENSP00000433871.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251458Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461866Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727234
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74302
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.989G>A (p.R330H) alteration is located in exon 5 (coding exon 5) of the CHRNA6 gene. This alteration results from a G to A substitution at nucleotide position 989, causing the arginine (R) at amino acid position 330 to be replaced by a histidine (H). 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