rs2241493

chr15-31070149-C-Achr15-31070149-C-Gchr15-31070149-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001252024.2(TRPM1):c.161G>T(p.Ser54Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S54N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPM1 NM_001252024.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025971413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM1	NM_001252024.2	c.161G>T	p.Ser54Ile	missense_variant	4/28	ENST00000256552.11
TRPM1	NM_001252020.2	c.212G>T	p.Ser71Ile	missense_variant	3/27
TRPM1	NM_002420.6	c.95G>T	p.Ser32Ile	missense_variant	3/27
TRPM1	NM_001252030.2	c.95G>T	p.Ser32Ile	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000256552.11	c.161G>T	p.Ser54Ile	missense_variant	4/28	1	NM_001252024.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.19
Dann	Benign	0.87
DEOGEN2	Benign	0.069	T;.;.;T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.30	T;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.026	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.;.;.;.;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.21	N;N;N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.18	T;T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;D;T;D
Polyphen		0.010	B;.;.;.;.;.
Vest4		0.064
MutPred		0.19		Loss of glycosylation at S32 (P = 0.0244);.;.;Loss of glycosylation at S32 (P = 0.0244);Loss of glycosylation at S32 (P = 0.0244);Loss of glycosylation at S32 (P = 0.0244);
MVP		0.081
MPC		0.25
ClinPred		0.076	T
GERP RS		-1.7
Varity_R		0.041
gMVP		0.22

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

Other links and lift over

dbSNP: rs2241493; hg19: chr15-31362352;