rs2288242
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001252024.2(TRPM1):āc.2406T>Cā(p.Asn802=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 1,613,820 control chromosomes in the GnomAD database, including 549,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.78 ( 47210 hom., cov: 33)
Exomes š: 0.83 ( 501828 hom. )
Consequence
TRPM1
NM_001252024.2 synonymous
NM_001252024.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.733
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 15-31038077-A-G is Benign according to our data. Variant chr15-31038077-A-G is described in ClinVar as [Benign]. Clinvar id is 315511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31038077-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.733 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPM1 | NM_001252024.2 | c.2406T>C | p.Asn802= | synonymous_variant | 19/28 | ENST00000256552.11 | NP_001238953.1 | |
TRPM1 | NM_001252020.2 | c.2457T>C | p.Asn819= | synonymous_variant | 18/27 | NP_001238949.1 | ||
TRPM1 | NM_002420.6 | c.2340T>C | p.Asn780= | synonymous_variant | 18/27 | NP_002411.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRPM1 | ENST00000256552.11 | c.2406T>C | p.Asn802= | synonymous_variant | 19/28 | 1 | NM_001252024.2 | ENSP00000256552 | P4 |
Frequencies
GnomAD3 genomes AF: 0.782 AC: 118893AN: 152068Hom.: 47171 Cov.: 33
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GnomAD3 exomes AF: 0.819 AC: 204223AN: 249378Hom.: 84659 AF XY: 0.812 AC XY: 109852AN XY: 135298
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GnomAD4 exome AF: 0.827 AC: 1208157AN: 1461634Hom.: 501828 Cov.: 48 AF XY: 0.822 AC XY: 597610AN XY: 727118
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GnomAD4 genome AF: 0.782 AC: 118986AN: 152186Hom.: 47210 Cov.: 33 AF XY: 0.782 AC XY: 58195AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Congenital stationary night blindness 1C Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at