15-31001571-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001252024.2(TRPM1):c.*251A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 563,636 control chromosomes in the GnomAD database, including 11,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2610 hom., cov: 32)
Exomes 𝑓: 0.19 ( 8758 hom. )
Consequence
TRPM1
NM_001252024.2 3_prime_UTR
NM_001252024.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.242
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 15-31001571-T-C is Benign according to our data. Variant chr15-31001571-T-C is described in ClinVar as [Benign]. Clinvar id is 315484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPM1 | NM_001252024.2 | c.*251A>G | 3_prime_UTR_variant | 28/28 | ENST00000256552.11 | NP_001238953.1 | ||
TRPM1 | NM_001252020.2 | c.*251A>G | 3_prime_UTR_variant | 27/27 | NP_001238949.1 | |||
TRPM1 | NM_002420.6 | c.*251A>G | 3_prime_UTR_variant | 27/27 | NP_002411.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRPM1 | ENST00000256552.11 | c.*251A>G | 3_prime_UTR_variant | 28/28 | 1 | NM_001252024.2 | ENSP00000256552 | P4 | ||
ENST00000665655.1 | n.71+9330T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.162 AC: 24649AN: 152062Hom.: 2609 Cov.: 32
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GnomAD4 exome AF: 0.192 AC: 79081AN: 411456Hom.: 8758 Cov.: 3 AF XY: 0.189 AC XY: 41504AN XY: 219908
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GnomAD4 genome AF: 0.162 AC: 24651AN: 152180Hom.: 2610 Cov.: 32 AF XY: 0.161 AC XY: 11989AN XY: 74408
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2019 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Congenital stationary night blindness 1C Benign:1
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