Variant rs770561064 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_002420.6(TRPM1):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000622 in 1,608,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

TRPM1
NM_002420.6 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.0580

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 3 pathogenic variants. Next in-frame start position is after 210 CDS bases. Genomic position: 31070034. Lost 0.044 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-31076919-C-T is Pathogenic according to our data. Variant chr15-31076919-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191053.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2 link	c.69G>A	p.Met23Ile	missense_variant	Exon 3 of 28	ENST00000256552.11	NP_001238953.1	Q7Z4N2-6
TRPM1	NM_002420.6 link	c.3G>A	p.Met1?	start_lost	Exon 2 of 27		NP_002411.3	Q7Z4N2-1
TRPM1	NM_001252030.2 link	c.3G>A	p.Met1?	start_lost	Exon 2 of 3		NP_001238959.1	Q7Z4N2-7
TRPM1	NM_001252020.2 link	c.120G>A	p.Met40Ile	missense_variant	Exon 2 of 27		NP_001238949.1	Q7Z4N2-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11 link	c.69G>A	p.Met23Ile	missense_variant	Exon 3 of 28	1	NM_001252024.2	ENSP00000256552.7		Q7Z4N2-6

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000112

AC:

AN:

249536

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000604

AC:

AN:

1456104

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

724860

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000343

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000497

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.23

DANN

Benign

0.85

DEOGEN2

Benign

0.073

T;.;.;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.055

LIST_S2

Uncertain

0.90

D;T;T;D;D;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.52

D;T;T;D;D;D

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.27

N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.27

T;D;D;T;T;D

Sift4G

Benign

0.37

T;D;D;D;T;D

Polyphen

0.0010

B;.;.;.;.;.

Vest4

0.074

MutPred

0.94

Gain of methylation at K2 (P = 0.0305);.;.;Gain of methylation at K2 (P = 0.0305);Gain of methylation at K2 (P = 0.0305);Gain of methylation at K2 (P = 0.0305);

MVP

0.22

MPC

0.23

ClinPred

0.48

GERP RS

-11

Varity_R

0.097

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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