chr20-63356386-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000744.7(CHRNA4):c.258C>A(p.Asn86Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,128 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 (★). Synonymous variant affecting the same amino acid position (i.e. N86N) has been classified as Likely benign.
Frequency
Consequence
NM_000744.7 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 |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.258C>A | p.Asn86Lys | missense_variant | 3/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.-289C>A | 5_prime_UTR_variant | 3/6 | |||
CHRNA4 | NR_046317.2 | n.442C>A | non_coding_transcript_exon_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.258C>A | p.Asn86Lys | missense_variant | 3/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000439 AC: 1AN: 227686Hom.: 0 AF XY: 0.00000813 AC XY: 1AN XY: 122934
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1448128Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2AN XY: 718744
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 11, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at