15-31070149-C-T

Position:

chr15-31070149-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001252024.2(TRPM1):c.161G>A(p.Ser54Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,992 control chromosomes in the GnomAD database, including 527,388 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48569 hom., cov: 32)

Exomes 𝑓: 0.81 ( 478819 hom. )

Consequence

TRPM1
NM_001252024.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.642

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.61148E-7).

BP6

Variant 15-31070149-C-T is Benign according to our data. Variant chr15-31070149-C-T is described in ClinVar as [Benign]. Clinvar id is 196343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-31070149-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPM1	NM_001252024.2 linkuse as main transcript	c.161G>A	p.Ser54Asn	missense_variant	4/28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2 linkuse as main transcript	c.212G>A	p.Ser71Asn	missense_variant	3/27		NP_001238949.1
TRPM1	NM_002420.6 linkuse as main transcript	c.95G>A	p.Ser32Asn	missense_variant	3/27		NP_002411.3
TRPM1	NM_001252030.2 linkuse as main transcript	c.95G>A	p.Ser32Asn	missense_variant	3/3		NP_001238959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11 linkuse as main transcript	c.161G>A	p.Ser54Asn	missense_variant	4/28	1	NM_001252024.2	ENSP00000256552	P4	Q7Z4N2-6

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121200

AN:

151996

Hom.:

48525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.754

Gnomad AMI

AF:

0.638

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.813

Gnomad EAS

AF:

0.927

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.814

GnomAD3 exomes

AF:

0.806

AC:

201110

AN:

249460

Hom.:

81955

AF XY:

0.795

AC XY:

107536

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.911

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.949

Gnomad SAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.783

Gnomad NFE exome

AF:

0.807

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.808

AC:

1180560

AN:

1461878

Hom.:

478819

Cov.:

AF XY:

0.802

AC XY:

583244

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.743

Gnomad4 AMR exome

AF:

0.903

Gnomad4 ASJ exome

AF:

0.810

Gnomad4 EAS exome

AF:

0.907

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.786

Gnomad4 NFE exome

AF:

0.816

Gnomad4 OTH exome

AF:

0.801

GnomAD4 genome

AF:

0.797

AC:

121299

AN:

152114

Hom.:

48569

Cov.:

AF XY:

0.794

AC XY:

59069

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.754

Gnomad4 AMR

AF:

0.866

Gnomad4 ASJ

AF:

0.813

Gnomad4 EAS

AF:

0.927

Gnomad4 SAS

AF:

0.670

Gnomad4 FIN

AF:

0.776

Gnomad4 NFE

AF:

0.812

Gnomad4 OTH

AF:

0.815

Alfa

AF:

0.809

Hom.:

126174

Bravo

AF:

0.806

TwinsUK

AF:

0.814

AC:

3019

ALSPAC

AF:

0.812

AC:

3131

ESP6500AA

AF:

0.754

AC:

2992

ESP6500EA

AF:

0.811

AC:

6759

ExAC

AF:

0.799

AC:

96541

Asia WGS

AF:

0.768

AC:

2672

AN:

3478

EpiCase

AF:

0.807

EpiControl

AF:

0.807

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital stationary night blindness 1C

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 25, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.013

DANN

Benign

0.74

DEOGEN2

Benign

0.071

T;.;.;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.015

T;T;T;T;T;T

MetaRNN

Benign

6.6e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.97

N;.;.;.;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

0.40

N;N;N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.51

T;T;T;T;T;T

Sift4G

Benign

0.53

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.028

MPC

0.19

ClinPred

0.0025

GERP RS

-1.7

Varity_R

0.027

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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