rs75638145

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The ENST00000558445.6(TRPM1):c.16C>T(p.Arg6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,534,778 control chromosomes in the GnomAD database, including 15,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1047 hom., cov: 33)

Exomes 𝑓: 0.14 ( 13960 hom. )

Consequence

TRPM1
ENST00000558445.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.33

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003954917).

BP6

Variant 15-31160944-G-A is Benign according to our data. Variant chr15-31160944-G-A is described in ClinVar as [Benign]. Clinvar id is 1297788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252020.2 link	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 27		NP_001238949.1	Q7Z4N2-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000558445.6 link	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 27	1		ENSP00000452946.2		Q7Z4N2-5H0YKU7
TRPM1	ENST00000559177.6 link	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 8	5		ENSP00000453477.2		H0YM61

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15999

AN:

152152

Hom.:

1049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.0581

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.102

AC:

13117

AN:

128012

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.0414

Gnomad AMR exome

AF:

0.0859

Gnomad ASJ exome

AF:

0.0985

Gnomad EAS exome

AF:

0.0181

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.136

AC:

187827

AN:

1382506

Hom.:

13960

Cov.:

AF XY:

0.134

AC XY:

91470

AN XY:

682198

show subpopulations

African (AFR)

AF:

0.0431

AC:

1361

AN:

31584

American (AMR)

AF:

0.0892

AC:

3183

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.0945

AC:

2379

AN:

25168

East Asian (EAS)

AF:

0.0125

AC:

445

AN:

35734

South Asian (SAS)

AF:

0.0729

AC:

5775

AN:

79214

European-Finnish (FIN)

AF:

0.167

AC:

5595

AN:

33460

Middle Eastern (MID)

AF:

0.146

AC:

833

AN:

5688

European-Non Finnish (NFE)

AF:

0.149

AC:

160881

AN:

1078112

Other (OTH)

AF:

0.127

AC:

7375

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

8807

17613

26420

35226

44033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.105

AC:

15990

AN:

152272

Hom.:

1047

Cov.:

AF XY:

0.105

AC XY:

7804

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0463

AC:

1925

AN:

41568

American (AMR)

AF:

0.109

AC:

1674

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

334

AN:

3470

East Asian (EAS)

AF:

0.0155

AC:

AN:

5176

South Asian (SAS)

AF:

0.0580

AC:

280

AN:

4830

European-Finnish (FIN)

AF:

0.162

AC:

1719

AN:

10598

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9616

AN:

68016

Other (OTH)

AF:

0.124

AC:

263

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

722

1445

2167

2890

3612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.122

Hom.:

265

Bravo

AF:

0.0999

TwinsUK

AF:

0.152

AC:

564

ALSPAC

AF:

0.148

AC:

569

ExAC

AF:

0.0672

AC:

1104

Asia WGS

AF:

0.0440

AC:

152

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2021

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

PhyloP100

2.3

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.84

REVEL

Benign

0.067

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Vest4

0.14

MPC

0.75

ClinPred

0.045

GERP RS

-0.92

PromoterAI

-0.036

Neutral

(source)

gMVP

0.33

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

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

Publications

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rs75638145

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