3-142806178-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001251845.2(TRPC1):āc.2325A>Gā(p.Ile775Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000068 ( 0 hom. )
Consequence
TRPC1
NM_001251845.2 missense
NM_001251845.2 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.91
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 -5 ACMG points.
PP2
Missense variant where missense usually causes diseases, TRPC1
BP4
Computational evidence support a benign effect (MetaRNN=0.11028445).
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPC1 | NM_001251845.2 | c.2325A>G | p.Ile775Met | missense_variant | 13/13 | ENST00000476941.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPC1 | ENST00000476941.6 | c.2325A>G | p.Ile775Met | missense_variant | 13/13 | 1 | NM_001251845.2 | P1 | |
TRPC1 | ENST00000273482.10 | c.2223A>G | p.Ile741Met | missense_variant | 12/12 | 1 | |||
TRPC1 | ENST00000698238.1 | c.2634A>G | p.Ile878Met | missense_variant | 13/13 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250992Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135630
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461408Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56AN XY: 726958
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74370
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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 | Jan 09, 2024 | The c.2223A>G (p.I741M) alteration is located in exon 12 (coding exon 12) of the TRPC1 gene. This alteration results from a A to G substitution at nucleotide position 2223, causing the isoleucine (I) at amino acid position 741 to be replaced by a methionine (M). 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
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of disorder (P = 0.0076);.;.;
MVP
MPC
ClinPred
D
GERP RS
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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