15-31038110-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001252024.2(TRPM1):c.2373T>C(p.Tyr791Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,592 control chromosomes in the GnomAD database, including 46,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4502 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42039 hom. )

Consequence

TRPM1
NM_001252024.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.988

Publications

12 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-31038110-A-G is Benign according to our data. Variant chr15-31038110-A-G is described in ClinVar as [Benign]. Clinvar id is 315512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2 link	c.2373T>C	p.Tyr791Tyr	synonymous_variant	Exon 19 of 28	ENST00000256552.11	NP_001238953.1	Q7Z4N2-6
TRPM1	NM_001252020.2 link	c.2424T>C	p.Tyr808Tyr	synonymous_variant	Exon 18 of 27		NP_001238949.1	Q7Z4N2-5
TRPM1	NM_002420.6 link	c.2307T>C	p.Tyr769Tyr	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.2373T>C	p.Tyr791Tyr	synonymous_variant	Exon 19 of 28	1	NM_001252024.2	ENSP00000256552.7		Q7Z4N2-6

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36309

AN:

152022

Hom.:

4496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.253

GnomAD2 exomes

AF:

0.226

AC:

56427

AN:

249138

AF XY:

0.226

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.00863

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.235

AC:

343354

AN:

1461452

Hom.:

42039

Cov.:

AF XY:

0.233

AC XY:

169192

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.263

AC:

8809

AN:

33468

American (AMR)

AF:

0.269

AC:

12007

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6131

AN:

26132

East Asian (EAS)

AF:

0.0220

AC:

874

AN:

39694

South Asian (SAS)

AF:

0.160

AC:

13774

AN:

86244

European-Finnish (FIN)

AF:

0.259

AC:

13806

AN:

53400

Middle Eastern (MID)

AF:

0.266

AC:

1534

AN:

5768

European-Non Finnish (NFE)

AF:

0.246

AC:

273079

AN:

1111656

Other (OTH)

AF:

0.221

AC:

13340

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12946

25892

38838

51784

64730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.239

AC:

36361

AN:

152140

Hom.:

4502

Cov.:

AF XY:

0.238

AC XY:

17703

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.258

AC:

10707

AN:

41500

American (AMR)

AF:

0.251

AC:

3834

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

802

AN:

3472

East Asian (EAS)

AF:

0.0110

AC:

AN:

5186

South Asian (SAS)

AF:

0.148

AC:

713

AN:

4816

European-Finnish (FIN)

AF:

0.249

AC:

2636

AN:

10570

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16768

AN:

67988

Other (OTH)

AF:

0.253

AC:

536

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1414

2828

4241

5655

7069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.245

Hom.:

19709

Bravo

AF:

0.244

Asia WGS

AF:

0.0980

AC:

343

AN:

3478

EpiCase

AF:

0.252

EpiControl

AF:

0.259

ClinVar

Significance: Benign

Submissions summary: Benign:4

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:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.56

(source)

DANN

Benign

0.55

PhyloP100

-0.99

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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15-31038110-A-G

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