rs12708421

Variant names:

• chr15-31040036-C-A
• rs12708421
• NM_001252024.2:c.2316+82G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-31040036-C-A
• chr15-31040036-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.2316+82G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,228,044 control chromosomes in the GnomAD database, including 34,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4507 hom., cov: 32)
  • Exomes 𝑓: 0.23 (30206 hom.)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.501
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae)
• TRPM1-related retinopathy

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259720 (HGNC:58477):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-31040036-C-A is Benign according to our data. Variant chr15-31040036-C-A is described in ClinVar as Benign. ClinVar VariationId is 1266664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	NM_001252024.2	MANE Select	c.2316+82G>T		intron	N/A	NP_001238953.1
	TRPM1	NM_001252020.2		c.2367+82G>T		intron	N/A	NP_001238949.1
	TRPM1	NM_002420.6		c.2250+82G>T		intron	N/A	NP_002411.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.2316+82G>T		intron	N/A	ENSP00000256552.7
	TRPM1	ENST00000558445.6	TSL:1	c.2367+82G>T		intron	N/A	ENSP00000452946.2
	TRPM1	ENST00000397795.7	TSL:1	c.2250+82G>T		intron	N/A	ENSP00000380897.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36396 AN: 152026 Hom.: 4500 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.230 AC: 247605 AN: 1075900 Hom.: 30206 AF XY: 0.228 AC XY: 125375 AN XY: 550964

African (AFR) AF: 0.263 AC: 6783 AN: 25838

American (AMR) AF: 0.269 AC: 11283 AN: 41928

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 5504 AN: 23558

East Asian (EAS) AF: 0.0228 AC: 851 AN: 37300

South Asian (SAS) AF: 0.158 AC: 12232 AN: 77650

European-Finnish (FIN) AF: 0.258 AC: 12641 AN: 48976

Middle Eastern (MID) AF: 0.266 AC: 1302 AN: 4902

European-Non Finnish (NFE) AF: 0.243 AC: 186404 AN: 767902

Other (OTH) AF: 0.222 AC: 10605 AN: 47846

GnomAD4 genome AF: 0.240 AC: 36452 AN: 152144 Hom.: 4507 Cov.: 32 AF XY: 0.238 AC XY: 17734 AN XY: 74374

African (AFR) AF: 0.260 AC: 10802 AN: 41474

American (AMR) AF: 0.251 AC: 3840 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5186

South Asian (SAS) AF: 0.147 AC: 707 AN: 4820

European-Finnish (FIN) AF: 0.248 AC: 2621 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16780 AN: 67994

Other (OTH) AF: 0.254 AC: 536 AN: 2110

Alfa AF: 0.248 Hom.: 987

Bravo AF: 0.244

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs12708421; hg19: chr15-31332239;