rs4779816
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_002420.6(TRPM1):āc.2T>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
TRPM1
NM_002420.6 start_lost
NM_002420.6 start_lost
Scores
1
3
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0460
Genes affected
TRPM1 (HGNC:7146): (transient receptor potential cation channel subfamily M member 1) This gene encodes a member of the transient receptor potential melastatin subfamily of transient receptor potential ion channels. The encoded protein is a calcium permeable cation channel that is expressed in melanocytes and may play a role in melanin synthesis. Specific mutations in this gene are the cause autosomal recessive complete congenital stationary night blindness-1C. The expression of this protein is inversely correlated with melanoma aggressiveness and as such it is used as a prognostic marker for melanoma metastasis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 3 pathogenic variants. Next in-frame start position is after 71 codons. Genomic position: 31070033. Lost 0.044 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TRPM1 | NM_001252024.2 | c.68T>G | p.Met23Arg | missense_variant | Exon 3 of 28 | ENST00000256552.11 | NP_001238953.1 | |
| TRPM1 | NM_002420.6 | c.2T>G | p.Met1? | start_lost | Exon 2 of 27 | NP_002411.3 | ||
| TRPM1 | NM_001252030.2 | c.2T>G | p.Met1? | start_lost | Exon 2 of 3 | NP_001238959.1 | ||
| TRPM1 | NM_001252020.2 | c.119T>G | p.Met40Arg | missense_variant | Exon 2 of 27 | NP_001238949.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1456434Hom.: 0 Cov.: 34 AF XY: 0.00000552 AC XY: 4AN XY: 724964
GnomAD4 exome
AF:
AC:
8
AN:
1456434
Hom.:
Cov.:
34
AF XY:
AC XY:
4
AN XY:
724964
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
B;.;.;.;.;.
Vest4
MutPred
Loss of ubiquitination at K2 (P = 0.0168);.;.;Loss of ubiquitination at K2 (P = 0.0168);Loss of ubiquitination at K2 (P = 0.0168);Loss of ubiquitination at K2 (P = 0.0168);
MVP
MPC
0.32
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