15-31001571-T-C

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.242
Variant links:
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
TRPM1NM_001252024.2 linkuse as main transcriptc.*251A>G 3_prime_UTR_variant 28/28 ENST00000256552.11 NP_001238953.1
TRPM1NM_001252020.2 linkuse as main transcriptc.*251A>G 3_prime_UTR_variant 27/27 NP_001238949.1
TRPM1NM_002420.6 linkuse as main transcriptc.*251A>G 3_prime_UTR_variant 27/27 NP_002411.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRPM1ENST00000256552.11 linkuse as main transcriptc.*251A>G 3_prime_UTR_variant 28/281 NM_001252024.2 ENSP00000256552 P4Q7Z4N2-6
ENST00000665655.1 linkuse as main transcriptn.71+9330T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.162
AC:
24649
AN:
152062
Hom.:
2609
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0497
Gnomad AMI
AF:
0.161
Gnomad AMR
AF:
0.150
Gnomad ASJ
AF:
0.183
Gnomad EAS
AF:
0.00673
Gnomad SAS
AF:
0.113
Gnomad FIN
AF:
0.254
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.233
Gnomad OTH
AF:
0.176
GnomAD4 exome
AF:
0.192
AC:
79081
AN:
411456
Hom.:
8758
Cov.:
3
AF XY:
0.189
AC XY:
41504
AN XY:
219908
show subpopulations
Gnomad4 AFR exome
AF:
0.0503
Gnomad4 AMR exome
AF:
0.137
Gnomad4 ASJ exome
AF:
0.189
Gnomad4 EAS exome
AF:
0.00438
Gnomad4 SAS exome
AF:
0.117
Gnomad4 FIN exome
AF:
0.248
Gnomad4 NFE exome
AF:
0.231
Gnomad4 OTH exome
AF:
0.190
GnomAD4 genome
AF:
0.162
AC:
24651
AN:
152180
Hom.:
2610
Cov.:
32
AF XY:
0.161
AC XY:
11989
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.0497
Gnomad4 AMR
AF:
0.150
Gnomad4 ASJ
AF:
0.183
Gnomad4 EAS
AF:
0.00675
Gnomad4 SAS
AF:
0.114
Gnomad4 FIN
AF:
0.254
Gnomad4 NFE
AF:
0.233
Gnomad4 OTH
AF:
0.174
Alfa
AF:
0.210
Hom.:
4753
Bravo
AF:
0.152
Asia WGS
AF:
0.0560
AC:
197
AN:
3478

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 submitterclinical testingGeneDxJan 19, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Congenital stationary night blindness 1C Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.1
DANN
Benign
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17227989; hg19: chr15-31293774; API