chr11-3666549-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020402.4(CHRNA10):c.911C>T(p.Ala304Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,545,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
CHRNA10
NM_020402.4 missense
NM_020402.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 7.70
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23925841).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA10 | NM_020402.4 | c.911C>T | p.Ala304Val | missense_variant | 5/5 | ENST00000250699.2 | |
CHRNA10 | NM_001303034.2 | c.293C>T | p.Ala98Val | missense_variant | 5/5 | ||
CHRNA10 | NM_001303035.2 | c.293C>T | p.Ala98Val | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA10 | ENST00000250699.2 | c.911C>T | p.Ala304Val | missense_variant | 5/5 | 1 | NM_020402.4 | P1 | |
CHRNA10 | ENST00000534359.1 | c.364C>T | p.Pro122Ser | missense_variant | 5/5 | 1 | |||
CHRNA10 | ENST00000526599.1 | c.*682C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000602 AC: 12AN: 199492Hom.: 0 AF XY: 0.0000283 AC XY: 3AN XY: 105876
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GnomAD4 exome AF: 0.0000230 AC: 32AN: 1393736Hom.: 0 Cov.: 30 AF XY: 0.0000161 AC XY: 11AN XY: 685132
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74336
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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 | Aug 10, 2021 | The c.911C>T (p.A304V) alteration is located in exon 5 (coding exon 5) of the CHRNA10 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the alanine (A) at amino acid position 304 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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