rs2241493

Variant names:

• chr15-31070149-C-T
• rs2241493
• NM_001252024.2:c.161G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-31070149-C-T
• chr15-31070149-C-A
• chr15-31070149-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 16/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.642
• Publications: 39 publications found

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: Labcorp Genetics (formerly Invitae), G2P
• TRPM1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 196343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252024.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	NM_001252024.2	MANE Select	c.161G>A	p.Ser54Asn	missense	Exon 4 of 28	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.212G>A	p.Ser71Asn	missense	Exon 3 of 27	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.95G>A	p.Ser32Asn	missense	Exon 3 of 27	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.161G>A	p.Ser54Asn	missense	Exon 4 of 28	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.212G>A	p.Ser71Asn	missense	Exon 3 of 27	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.95G>A	p.Ser32Asn	missense	Exon 3 of 27	ENSP00000380897.2	Q7Z4N2-1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121200 AN: 151996 Hom.: 48525 Cov.: 32

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

GnomAD2 exomes AF: 0.806 AC: 201110 AN: 249460 AF XY: 0.795

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 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.: 83 AF XY: 0.802 AC XY: 583244 AN XY: 727242

African (AFR) AF: 0.743 AC: 24885 AN: 33480

American (AMR) AF: 0.903 AC: 40408 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 21171 AN: 26132

East Asian (EAS) AF: 0.907 AC: 36011 AN: 39700

South Asian (SAS) AF: 0.652 AC: 56279 AN: 86258

European-Finnish (FIN) AF: 0.786 AC: 41983 AN: 53420

Middle Eastern (MID) AF: 0.721 AC: 4154 AN: 5764

European-Non Finnish (NFE) AF: 0.816 AC: 907295 AN: 1112004

Other (OTH) AF: 0.801 AC: 48374 AN: 60396

GnomAD4 genome AF: 0.797 AC: 121299 AN: 152114 Hom.: 48569 Cov.: 32 AF XY: 0.794 AC XY: 59069 AN XY: 74350

African (AFR) AF: 0.754 AC: 31283 AN: 41474

American (AMR) AF: 0.866 AC: 13241 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2818 AN: 3466

East Asian (EAS) AF: 0.927 AC: 4810 AN: 5188

South Asian (SAS) AF: 0.670 AC: 3226 AN: 4812

European-Finnish (FIN) AF: 0.776 AC: 8204 AN: 10568

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55195 AN: 68006

Other (OTH) AF: 0.815 AC: 1718 AN: 2108

Alfa AF: 0.808 Hom.: 235954

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Congenital stationary night blindness 1C (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.013
DANN	Benign	0.74
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.015	T
MetaRNN	Benign	6.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N
PhyloP100		-0.64
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.056
Sift	Benign	0.51	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.19
ClinPred		0.0025	T
GERP RS		-1.7
Varity_R		0.027
gMVP		0.13
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241493; hg19: chr15-31362352; COSMIC: COSV56636099; COSMIC: COSV56636099;