15-31037741-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001252024.2(TRPM1):c.2541C>T(p.Asn847Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,938 control chromosomes in the GnomAD database, including 13,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1248 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12334 hom. )

Consequence

TRPM1
NM_001252024.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.470

Publications

13 publications found

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 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

TRPM1 links:

ENSG00000259720 (HGNC:58477):

ENSG00000259720 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 15-31037741-G-A is Benign according to our data. Variant chr15-31037741-G-A is described in ClinVar as [Benign]. Clinvar id is 315509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2 link	c.2541C>T	p.Asn847Asn	synonymous_variant	Exon 20 of 28	ENST00000256552.11	NP_001238953.1	Q7Z4N2-6
TRPM1	NM_001252020.2 link	c.2592C>T	p.Asn864Asn	synonymous_variant	Exon 19 of 27		NP_001238949.1	Q7Z4N2-5
TRPM1	NM_002420.6 link	c.2475C>T	p.Asn825Asn	synonymous_variant	Exon 19 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.2541C>T	p.Asn847Asn	synonymous_variant	Exon 20 of 28	1	NM_001252024.2	ENSP00000256552.7		Q7Z4N2-6

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18468

AN:

152084

Hom.:

1247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.0782

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.110

GnomAD2 exomes

AF:

0.129

AC:

32269

AN:

249580

AF XY:

0.128

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.0835

Gnomad EAS exome

AF:

0.00834

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.126

AC:

183933

AN:

1461736

Hom.:

12334

Cov.:

AF XY:

0.125

AC XY:

91064

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.106

AC:

3565

AN:

33480

American (AMR)

AF:

0.194

AC:

8659

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

2283

AN:

26134

East Asian (EAS)

AF:

0.0217

AC:

863

AN:

39700

South Asian (SAS)

AF:

0.116

AC:

10029

AN:

86254

European-Finnish (FIN)

AF:

0.170

AC:

9082

AN:

53420

Middle Eastern (MID)

AF:

0.148

AC:

855

AN:

5768

European-Non Finnish (NFE)

AF:

0.128

AC:

141840

AN:

1111872

Other (OTH)

AF:

0.112

AC:

6757

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

9410

18820

28231

37641

47051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.121

AC:

18492

AN:

152202

Hom.:

1248

Cov.:

AF XY:

0.124

AC XY:

9204

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.109

AC:

4518

AN:

41510

American (AMR)

AF:

0.155

AC:

2365

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0782

AC:

271

AN:

3466

East Asian (EAS)

AF:

0.0106

AC:

AN:

5190

South Asian (SAS)

AF:

0.111

AC:

535

AN:

4826

European-Finnish (FIN)

AF:

0.164

AC:

1737

AN:

10594

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8605

AN:

68006

Other (OTH)

AF:

0.111

AC:

235

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

824

1648

2473

3297

4121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.125

Hom.:

2240

Bravo

AF:

0.121

Asia WGS

AF:

0.0720

AC:

254

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital stationary night blindness 1C

Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.028

(source)

DANN

Benign

0.81

PhyloP100

-0.47

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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15-31037741-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over