chr2-233945896-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_024080.5(TRPM8):c.740G>C(p.Arg247Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0462 in 1,613,728 control chromosomes in the GnomAD database, including 1,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.041 ( 163 hom., cov: 33)
Exomes 𝑓: 0.047 ( 1814 hom. )
Consequence
TRPM8
NM_024080.5 missense
NM_024080.5 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 7.16
Genes affected
TRPM8 (HGNC:17961): (transient receptor potential cation channel subfamily M member 8) Predicted to enable ligand-gated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within several processes, including cellular calcium ion homeostasis; response to cold; and thermoception. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0030798316).
BP6
?
Variant 2-233945896-G-C is Benign according to our data. Variant chr2-233945896-G-C is described in ClinVar as [Benign]. Clinvar id is 1246736.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM8 | NM_024080.5 | c.740G>C | p.Arg247Thr | missense_variant | 7/26 | ENST00000324695.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM8 | ENST00000324695.9 | c.740G>C | p.Arg247Thr | missense_variant | 7/26 | 1 | NM_024080.5 | P1 | |
TRPM8 | ENST00000444298.5 | c.740G>C | p.Arg247Thr | missense_variant, NMD_transcript_variant | 7/25 | 1 | |||
TRPM8 | ENST00000433712.6 | c.17G>C | p.Arg6Thr | missense_variant | 7/24 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0410 AC: 6238AN: 152094Hom.: 158 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0500 AC: 12564AN: 251322Hom.: 379 AF XY: 0.0479 AC XY: 6504AN XY: 135814
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GnomAD4 exome AF: 0.0468 AC: 68383AN: 1461516Hom.: 1814 Cov.: 30 AF XY: 0.0464 AC XY: 33719AN XY: 727086
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GnomAD4 genome ? AF: 0.0411 AC: 6250AN: 152212Hom.: 163 Cov.: 33 AF XY: 0.0407 AC XY: 3030AN XY: 74410
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107
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?
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5707
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2019 | This variant is associated with the following publications: (PMID: 27421018) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
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