rs2288242

chr15-31038077-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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

• 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:4
• 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]

(HGNC:):

ACMG classification

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	UniProt
TRPM1	NM_001252024.2	c.2406T>C	p.Asn802=	synonymous_variant	19/28	ENST00000256552.11
TRPM1	NM_001252020.2	c.2457T>C	p.Asn819=	synonymous_variant	18/27
TRPM1	NM_002420.6	c.2340T>C	p.Asn780=	synonymous_variant	18/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000256552.11	c.2406T>C	p.Asn802=	synonymous_variant	19/28	1	NM_001252024.2	P4

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

GnomAD3 exomes AF: 0.819 AC: 204223 AN: 249378 Hom.: 84659 AF XY: 0.812 AC XY: 109852 AN XY: 135298

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 SAS exome AF: 0.664

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

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.880

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.810

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

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.804

Alfa AF: 0.821 Hom.: 87806

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.0070
Dann	Benign	0.50

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

Other links and lift over

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