chr4-121879767-T-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2
The NM_001130698.2(TRPC3):c.2735A>C(p.Lys912Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00139 in 1,610,172 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00083 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 47 hom. )
Consequence
TRPC3
NM_001130698.2 missense
NM_001130698.2 missense
Scores
1
7
7
Clinical Significance
Conservation
PhyloP100: 4.26
Genes affected
TRPC3 (HGNC:12335): (transient receptor potential cation channel subfamily C member 3) 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 Benign. Variant got -13 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRPC3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006897241).
BP6
?
Variant 4-121879767-T-G is Benign according to our data. Variant chr4-121879767-T-G is described in ClinVar as [Benign]. Clinvar id is 2044150.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000827 (126/152314) while in subpopulation SAS AF= 0.0253 (122/4826). AF 95% confidence interval is 0.0216. There are 2 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 127 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPC3 | NM_001130698.2 | c.2735A>C | p.Lys912Thr | missense_variant | 12/12 | ENST00000379645.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPC3 | ENST00000379645.8 | c.2735A>C | p.Lys912Thr | missense_variant | 12/12 | 1 | NM_001130698.2 | P4 | |
TRPC3 | ENST00000264811.9 | c.2516A>C | p.Lys839Thr | missense_variant | 11/11 | 1 | A2 | ||
TRPC3 | ENST00000513531.1 | c.2351A>C | p.Lys784Thr | missense_variant | 10/10 | 1 | |||
TRPC3 | ENST00000506449.1 | c.*1743A>C | 3_prime_UTR_variant, NMD_transcript_variant | 12/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000834 AC: 127AN: 152196Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00296 AC: 731AN: 246914Hom.: 15 AF XY: 0.00423 AC XY: 565AN XY: 133526
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GnomAD4 exome AF: 0.00145 AC: 2119AN: 1457858Hom.: 47 Cov.: 30 AF XY: 0.00215 AC XY: 1558AN XY: 725154
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GnomAD4 genome ? AF: 0.000827 AC: 126AN: 152314Hom.: 2 Cov.: 32 AF XY: 0.00121 AC XY: 90AN XY: 74486
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ExAC
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417
Asia WGS
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3478
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 | Invitae | Aug 16, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Vest4
MVP
MPC
0.93
ClinPred
T
GERP RS
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