15-31037741-G-A

Variant names:

• chr15-31037741-G-A
• rs12911350
• NM_001252024.2:c.2541C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001252024.2(TRPM1):​c.2541C>T​(p.Asn847Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,938 control chromosomes in the GnomAD database, including 13,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1248 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12334 hom.)
• Consequence: TRPM1 NM_001252024.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.470
• Publications: 13 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

ENSG00000259720 (HGNC:58477):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 15-31037741-G-A is Benign according to our data. Variant chr15-31037741-G-A is described in ClinVar as Benign. ClinVar VariationId is 315509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 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.2541C>T	p.Asn847Asn	synonymous	Exon 20 of 28	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.2592C>T	p.Asn864Asn	synonymous	Exon 19 of 27	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.2475C>T	p.Asn825Asn	synonymous	Exon 19 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.2541C>T	p.Asn847Asn	synonymous	Exon 20 of 28	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.2592C>T	p.Asn864Asn	synonymous	Exon 19 of 27	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.2475C>T	p.Asn825Asn	synonymous	Exon 19 of 27	ENSP00000380897.2	Q7Z4N2-1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18468 AN: 152084 Hom.: 1247 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0782

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.129 AC: 32269 AN: 249580 AF XY: 0.128

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.0835

Gnomad EAS exome AF: 0.00834

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.126 AC: 183933 AN: 1461736 Hom.: 12334 Cov.: 34 AF XY: 0.125 AC XY: 91064 AN XY: 727178

African (AFR) AF: 0.106 AC: 3565 AN: 33480

American (AMR) AF: 0.194 AC: 8659 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 2283 AN: 26134

East Asian (EAS) AF: 0.0217 AC: 863 AN: 39700

South Asian (SAS) AF: 0.116 AC: 10029 AN: 86254

European-Finnish (FIN) AF: 0.170 AC: 9082 AN: 53420

Middle Eastern (MID) AF: 0.148 AC: 855 AN: 5768

European-Non Finnish (NFE) AF: 0.128 AC: 141840 AN: 1111872

Other (OTH) AF: 0.112 AC: 6757 AN: 60384

GnomAD4 genome AF: 0.121 AC: 18492 AN: 152202 Hom.: 1248 Cov.: 33 AF XY: 0.124 AC XY: 9204 AN XY: 74428

African (AFR) AF: 0.109 AC: 4518 AN: 41510

American (AMR) AF: 0.155 AC: 2365 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0782 AC: 271 AN: 3466

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5190

South Asian (SAS) AF: 0.111 AC: 535 AN: 4826

European-Finnish (FIN) AF: 0.164 AC: 1737 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8605 AN: 68006

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.125 Hom.: 2240

Bravo AF: 0.121

Asia WGS AF: 0.0720 AC: 254 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.129

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.028
DANN	Benign	0.81
PhyloP100		-0.47
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs12911350; hg19: chr15-31329944; COSMIC: COSV56635643; COSMIC: COSV56635643;