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: Labcorp Genetics (formerly Invitae), G2P
• 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 ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252024.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	NM_001252024.2	MANE Select	c.2406T>C	p.Asn802Asn	synonymous	Exon 19 of 28	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.2457T>C	p.Asn819Asn	synonymous	Exon 18 of 27	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.2340T>C	p.Asn780Asn	synonymous	Exon 18 of 27	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.2406T>C	p.Asn802Asn	synonymous	Exon 19 of 28	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.2457T>C	p.Asn819Asn	synonymous	Exon 18 of 27	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.2340T>C	p.Asn780Asn	synonymous	Exon 18 of 27	ENSP00000380897.2	Q7Z4N2-1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Congenital stationary night blindness 1C (2)

Computational scores

Source: dbNSFP v4.9

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;