rs999572673
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017636.4(TRPM4):c.13G>A(p.Glu5Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E5Q) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TRPM4
NM_017636.4 missense
NM_017636.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 2.16
Publications
0 publications found
Genes affected
TRPM4 (HGNC:17993): (transient receptor potential cation channel subfamily M member 4) The protein encoded by this gene is a calcium-activated nonselective ion channel that mediates transport of monovalent cations across membranes, thereby depolarizing the membrane. The activity of the encoded protein increases with increasing intracellular calcium concentration, but this channel does not transport calcium. [provided by RefSeq, Mar 2016]
TRPM4 Gene-Disease associations (from GenCC):
- erythrokeratodermia variabilis et progressiva 6Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- progressive familial heart block type IBInheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- erythrokeratodermia variabilisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- progressive familial heart blockInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Brugada syndromeInheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26322138).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_017636.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TRPM4 | TSL:1 MANE Select | c.13G>A | p.Glu5Lys | missense | Exon 1 of 25 | ENSP00000252826.4 | Q8TD43-1 | ||
| TRPM4 | TSL:1 | c.13G>A | p.Glu5Lys | missense | Exon 1 of 24 | ENSP00000407492.1 | Q8TD43-3 | ||
| TRPM4 | TSL:1 | n.13G>A | non_coding_transcript_exon | Exon 1 of 23 | ENSP00000469893.1 | M0QYK7 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152190
Hom.:
Cov.:
31
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:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1382782Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 682348
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1382782
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
682348
African (AFR)
AF:
AC:
0
AN:
31552
American (AMR)
AF:
AC:
0
AN:
35666
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25154
East Asian (EAS)
AF:
AC:
0
AN:
35738
South Asian (SAS)
AF:
AC:
0
AN:
79146
European-Finnish (FIN)
AF:
AC:
0
AN:
34278
Middle Eastern (MID)
AF:
AC:
0
AN:
5024
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1078432
Other (OTH)
AF:
AC:
0
AN:
57792
GnomAD4 genome 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74336 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152190
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74336
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41450
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5182
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68032
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
1
-
Cardiovascular phenotype (1)
-
1
-
Progressive familial heart block type IB (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
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
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.