chr11-3667526-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000534359.1(CHRNA10):c.54G>A(p.Trp18Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000113 in 1,585,994 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
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000084 ( 0 hom. )
Consequence
CHRNA10
ENST00000534359.1 stop_gained
ENST00000534359.1 stop_gained
Scores
9
8
1
Clinical Significance
Conservation
PhyloP100: 6.07
Genes affected
CHRNA10 (HGNC:13800): (cholinergic receptor nicotinic alpha 10 subunit) Predicted to enable acetylcholine-gated cation-selective channel activity. Acts upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be located in membrane. Predicted to be active in cholinergic synapse and neuron projection. Predicted to be integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA10 | NM_020402.4 | c.601G>A | p.Glu201Lys | missense_variant | 4/5 | ENST00000250699.2 | |
CHRNA10 | NM_001303034.2 | c.-18G>A | 5_prime_UTR_variant | 4/5 | |||
CHRNA10 | NM_001303035.2 | c.-18G>A | 5_prime_UTR_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA10 | ENST00000534359.1 | c.54G>A | p.Trp18Ter | stop_gained | 4/5 | 1 | |||
CHRNA10 | ENST00000250699.2 | c.601G>A | p.Glu201Lys | missense_variant | 4/5 | 1 | NM_020402.4 | P1 | |
CHRNA10 | ENST00000526599.1 | c.*372G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152090Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000496 AC: 1AN: 201632Hom.: 0 AF XY: 0.00000885 AC XY: 1AN XY: 112968
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GnomAD4 exome AF: 0.00000837 AC: 12AN: 1433904Hom.: 0 Cov.: 32 AF XY: 0.00000841 AC XY: 6AN XY: 713212
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 152090Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74310
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2022 | The c.601G>A (p.E201K) alteration is located in exon 4 (coding exon 4) of the CHRNA10 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glutamic acid (E) at amino acid position 201 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
A;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0042);
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