15-31050541-C-T

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.1305G>A(p.Thr435Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,613,692 control chromosomes in the GnomAD database, including 252,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19500 hom., cov: 31)

Exomes 𝑓: 0.56 ( 232522 hom. )

Consequence

TRPM1
NM_001252024.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.87

Publications

25 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:

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=-0.81).

BP6

Variant 15-31050541-C-T is Benign according to our data. Variant chr15-31050541-C-T is described in ClinVar as Benign. ClinVar VariationId is 193856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TRPM1	NM_001252024.2 link	c.1305G>A	p.Thr435Thr	synonymous_variant	Exon 12 of 28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2 link	c.1356G>A	p.Thr452Thr	synonymous_variant	Exon 11 of 27		NP_001238949.1
TRPM1	NM_002420.6 link	c.1239G>A	p.Thr413Thr	synonymous_variant	Exon 11 of 27		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11 link	c.1305G>A	p.Thr435Thr	synonymous_variant	Exon 12 of 28	1	NM_001252024.2	ENSP00000256552.7

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72871

AN:

151764

Hom.:

19503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.574

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.941

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.505

GnomAD2 exomes

AF:

0.555

AC:

136961

AN:

246920

AF XY:

0.550

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.963

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.558

AC:

815022

AN:

1461810

Hom.:

232522

Cov.:

AF XY:

0.556

AC XY:

404090

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.214

AC:

7181

AN:

33480

American (AMR)

AF:

0.599

AC:

26778

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

14700

AN:

26136

East Asian (EAS)

AF:

0.909

AC:

36095

AN:

39696

South Asian (SAS)

AF:

0.478

AC:

41213

AN:

86258

European-Finnish (FIN)

AF:

0.540

AC:

28815

AN:

53398

Middle Eastern (MID)

AF:

0.463

AC:

2673

AN:

5768

European-Non Finnish (NFE)

AF:

0.561

AC:

623961

AN:

1111974

Other (OTH)

AF:

0.556

AC:

33606

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

22569

45138

67707

90276

112845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17444

34888

52332

69776

87220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.480

AC:

72893

AN:

151882

Hom.:

19500

Cov.:

AF XY:

0.483

AC XY:

35854

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.235

AC:

9716

AN:

41418

American (AMR)

AF:

0.574

AC:

8762

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

1962

AN:

3468

East Asian (EAS)

AF:

0.941

AC:

4850

AN:

5156

South Asian (SAS)

AF:

0.505

AC:

2423

AN:

4794

European-Finnish (FIN)

AF:

0.542

AC:

5720

AN:

10548

Middle Eastern (MID)

AF:

0.500

AC:

145

AN:

290

European-Non Finnish (NFE)

AF:

0.558

AC:

37882

AN:

67926

Other (OTH)

AF:

0.505

AC:

1063

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1712

3424

5136

6848

8560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.527

Hom.:

39871

Bravo

AF:

0.474

Asia WGS

AF:

0.653

AC:

2267

AN:

3478

EpiCase

AF:

0.552

EpiControl

AF:

0.543

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not specified

Benign:1

Mar 11, 2015

Eurofins Ntd Llc (ga)

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

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.63

PhyloP100

-1.9

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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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