rs36111323
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004621.6(TRPC6):c.1211C>T(p.Ala404Val) variant causes a missense change. The variant allele was found at a frequency of 0.111 in 1,614,072 control chromosomes in the GnomAD database, including 10,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A404A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.083 ( 716 hom., cov: 33)
Exomes 𝑓: 0.11 ( 10195 hom. )
Consequence
TRPC6
NM_004621.6 missense
NM_004621.6 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.84
Genes affected
TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0019279122).
BP6
?
Variant 11-101489019-G-A is Benign according to our data. Variant chr11-101489019-G-A is described in ClinVar as [Benign]. Clinvar id is 259454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPC6 | NM_004621.6 | c.1211C>T | p.Ala404Val | missense_variant | 4/13 | ENST00000344327.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPC6 | ENST00000344327.8 | c.1211C>T | p.Ala404Val | missense_variant | 4/13 | 1 | NM_004621.6 | P1 | |
TRPC6 | ENST00000348423.8 | c.946-5854C>T | intron_variant | 1 | |||||
TRPC6 | ENST00000360497.4 | c.1128+2537C>T | intron_variant | 1 | |||||
TRPC6 | ENST00000532133.5 | c.1211C>T | p.Ala404Val | missense_variant | 4/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0830 AC: 12635AN: 152164Hom.: 714 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
12635
AN:
152164
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0954 AC: 23989AN: 251350Hom.: 1357 AF XY: 0.101 AC XY: 13763AN XY: 135842
GnomAD3 exomes
AF:
AC:
23989
AN:
251350
Hom.:
AF XY:
AC XY:
13763
AN XY:
135842
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.114 AC: 167280AN: 1461790Hom.: 10195 Cov.: 31 AF XY: 0.116 AC XY: 84129AN XY: 727192
GnomAD4 exome
AF:
AC:
167280
AN:
1461790
Hom.:
Cov.:
31
AF XY:
AC XY:
84129
AN XY:
727192
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0829 AC: 12628AN: 152282Hom.: 716 Cov.: 33 AF XY: 0.0825 AC XY: 6146AN XY: 74468
GnomAD4 genome
?
AF:
AC:
12628
AN:
152282
Hom.:
Cov.:
33
AF XY:
AC XY:
6146
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
420
ALSPAC
AF:
AC:
456
ESP6500AA
AF:
AC:
100
ESP6500EA
AF:
AC:
1047
ExAC
?
AF:
AC:
11961
Asia WGS
AF:
AC:
172
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 14, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2019 | This variant is associated with the following publications: (PMID: 19701773, 26127002, 26892346, 28476686) - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 21. Only high quality variants are reported. - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 27, 2022 | - - |
Focal segmental glomerulosclerosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at