rs75638145

chr15-31160944-G-Achr15-31160944-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 10/16 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
TRPM1	NM_001252020.2	c.16C>T	p.Arg6Trp	missense_variant	1/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000558445.6	c.16C>T	p.Arg6Trp	missense_variant	1/27	1		A2
TRPM1	ENST00000559177.6	c.16C>T	p.Arg6Trp	missense_variant	1/8	5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15999 AN: 152152 Hom.: 1049 Cov.: 33

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

GnomAD3 exomes AF: 0.102 AC: 13117 AN: 128012 Hom.: 795 AF XY: 0.103 AC XY: 7251 AN XY: 70094

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 SAS exome AF: 0.0747

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.: 32 AF XY: 0.134 AC XY: 91470 AN XY: 682198

Gnomad4 AFR exome AF: 0.0431

Gnomad4 AMR exome AF: 0.0892

Gnomad4 ASJ exome AF: 0.0945

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.0729

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.105 AC: 15990 AN: 152272 Hom.: 1047 Cov.: 33 AF XY: 0.105 AC XY: 7804 AN XY: 74442

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.0155

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.124

Alfa AF: 0.124 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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.067
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Vest4		0.14
MPC		0.75
ClinPred		0.045	T
GERP RS		-0.92
gMVP		0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs75638145; hg19: chr15-31453147;