rs2288242

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.733

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]

TRPM1 links:

ENSG00000259720 (HGNC:):

ENSG00000259720 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2 link	c.2406T>C	p.Asn802Asn	synonymous_variant	Exon 19 of 28	ENST00000256552.11	NP_001238953.1	Q7Z4N2-6
TRPM1	NM_001252020.2 link	c.2457T>C	p.Asn819Asn	synonymous_variant	Exon 18 of 27		NP_001238949.1	Q7Z4N2-5
TRPM1	NM_002420.6 link	c.2340T>C	p.Asn780Asn	synonymous_variant	Exon 18 of 27		NP_002411.3	Q7Z4N2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11 link	c.2406T>C	p.Asn802Asn	synonymous_variant	Exon 19 of 28	1	NM_001252024.2	ENSP00000256552.7		Q7Z4N2-6

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

118893

AN:

152068

Hom.:

47171

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.822

AC XY:

597610

AN XY:

727118

show subpopulations

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.:

AF XY:

0.782

AC XY:

58195

AN XY:

74396

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over