chr3-142806198-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001251845.2(TRPC1):c.2345G>A(p.Arg782Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,612,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
TRPC1
NM_001251845.2 missense
NM_001251845.2 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 9.58
Genes affected
TRPC1 (HGNC:12333): (transient receptor potential cation channel subfamily C member 1) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, TRPC1
BS2
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPC1 | NM_001251845.2 | c.2345G>A | p.Arg782Gln | missense_variant | 13/13 | ENST00000476941.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPC1 | ENST00000476941.6 | c.2345G>A | p.Arg782Gln | missense_variant | 13/13 | 1 | NM_001251845.2 | P1 | |
TRPC1 | ENST00000273482.10 | c.2243G>A | p.Arg748Gln | missense_variant | 12/12 | 1 | |||
TRPC1 | ENST00000698238.1 | c.2654G>A | p.Arg885Gln | missense_variant | 13/13 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250838Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135564
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GnomAD4 exome AF: 0.0000199 AC: 29AN: 1460534Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15AN XY: 726368
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74258
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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 06, 2024 | The c.2243G>A (p.R748Q) alteration is located in exon 12 (coding exon 12) of the TRPC1 gene. This alteration results from a G to A substitution at nucleotide position 2243, causing the arginine (R) at amino acid position 748 to be replaced by a glutamine (Q). 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Benign
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0175);.;.;
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