rs2288242

Variant names:

• chr15-31038077-A-G
• rs2288242
• NM_001252024.2:c.2406T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001252024.2(TRPM1):​c.2406T>C​(p.Asn802Asn) 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47210 hom., cov: 33)
  • Exomes 𝑓: 0.83 (501828 hom.)
• Consequence: TRPM1 NM_001252024.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.733
• Publications: 22 publications found

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]

TRPM1 Gene-Disease associations (from GenCC):

• congenital stationary night blindness 1C

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• TRPM1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259720 (HGNC:58477):

ACMG classification

Our verdict: Benign. The variant received -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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar as Benign. Clinvar id is 315511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.2406T>C	p.Asn802Asn	synonymous_variant	Exon 19 of 28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2	c.2457T>C	p.Asn819Asn	synonymous_variant	Exon 18 of 27		NP_001238949.1
TRPM1	NM_002420.6	c.2340T>C	p.Asn780Asn	synonymous_variant	Exon 18 of 27		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.2406T>C	p.Asn802Asn	synonymous_variant	Exon 19 of 28	1	NM_001252024.2	ENSP00000256552.7

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118893 AN: 152068 Hom.: 47171 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.803

GnomAD2 exomes AF: 0.819 AC: 204223 AN: 249378 AF XY: 0.812

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.883

Gnomad ASJ exome AF: 0.831

Gnomad EAS exome AF: 0.973

Gnomad FIN exome AF: 0.849

Gnomad NFE exome AF: 0.836

Gnomad OTH exome AF: 0.817

GnomAD4 exome AF: 0.827 AC: 1208157 AN: 1461634 Hom.: 501828 Cov.: 48 AF XY: 0.822 AC XY: 597610 AN XY: 727118

African (AFR) AF: 0.619 AC: 20729 AN: 33474

American (AMR) AF: 0.880 AC: 39340 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 21781 AN: 26130

East Asian (EAS) AF: 0.932 AC: 37012 AN: 39694

South Asian (SAS) AF: 0.672 AC: 57972 AN: 86248

European-Finnish (FIN) AF: 0.851 AC: 45449 AN: 53412

Middle Eastern (MID) AF: 0.743 AC: 4285 AN: 5768

European-Non Finnish (NFE) AF: 0.839 AC: 932660 AN: 1111810

Other (OTH) AF: 0.810 AC: 48929 AN: 60382

GnomAD4 genome AF: 0.782 AC: 118986 AN: 152186 Hom.: 47210 Cov.: 33 AF XY: 0.782 AC XY: 58195 AN XY: 74396

African (AFR) AF: 0.633 AC: 26272 AN: 41484

American (AMR) AF: 0.853 AC: 13048 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2887 AN: 3468

East Asian (EAS) AF: 0.953 AC: 4943 AN: 5186

South Asian (SAS) AF: 0.686 AC: 3304 AN: 4818

European-Finnish (FIN) AF: 0.848 AC: 8988 AN: 10596

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56988 AN: 68022

Other (OTH) AF: 0.804 AC: 1697 AN: 2112

Alfa AF: 0.818 Hom.: 114017

Bravo AF: 0.781

Asia WGS AF: 0.780 AC: 2712 AN: 3478

EpiCase AF: 0.831

EpiControl AF: 0.833

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital stationary night blindness 1C Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0070
DANN	Benign	0.50
PhyloP100		-0.73
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2288242; hg19: chr15-31330280; COSMIC: COSV56632180; COSMIC: COSV56632180;