chr4-40354036-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_017581.4(CHRNA9):c.956T>C(p.Met319Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000662 in 1,614,196 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00070 ( 2 hom. )
Consequence
CHRNA9
NM_017581.4 missense
NM_017581.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
CHRNA9 (HGNC:14079): (cholinergic receptor nicotinic alpha 9 subunit) This gene is a member of the ligand-gated ionic channel family and nicotinic acetylcholine receptor gene superfamily. It encodes a plasma membrane protein that forms homo- or hetero-oligomeric divalent cation channels. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2696194).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA9 | NM_017581.4 | c.956T>C | p.Met319Thr | missense_variant | 5/5 | ENST00000310169.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA9 | ENST00000310169.3 | c.956T>C | p.Met319Thr | missense_variant | 5/5 | 1 | NM_017581.4 | P1 | |
CHRNA9 | ENST00000509518.1 | n.407T>C | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152246Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000140 AC: 35AN: 250196Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135278
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GnomAD4 exome AF: 0.000698 AC: 1021AN: 1461832Hom.: 2 Cov.: 34 AF XY: 0.000686 AC XY: 499AN XY: 727218
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GnomAD4 genome ? AF: 0.000308 AC: 47AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74514
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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 30, 2021 | The c.956T>C (p.M319T) alteration is located in exon 5 (coding exon 5) of the CHRNA9 gene. This alteration results from a T to C substitution at nucleotide position 956, causing the methionine (M) at amino acid position 319 to be replaced by a threonine (T). 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
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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