15-31038110-A-G

Variant names:

• chr15-31038110-A-G
• rs12913672
• NM_001252024.2:c.2373T>C

Variant summary

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

The NM_001252020.2(TRPM1):​c.2424T>C​(p.Tyr808Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,592 control chromosomes in the GnomAD database, including 46,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4502 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42039 hom.)
• Consequence: TRPM1 NM_001252020.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.988
• Publications: 12 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=-0.84).
• BP6: Variant 15-31038110-A-G is Benign according to our data. Variant chr15-31038110-A-G is described in ClinVar as Benign. ClinVar VariationId is 315512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252020.2. 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.2373T>C	p.Tyr791Tyr	synonymous	Exon 19 of 28	NP_001238953.1
	TRPM1	NM_001252020.2		c.2424T>C	p.Tyr808Tyr	synonymous	Exon 18 of 27	NP_001238949.1
	TRPM1	NM_002420.6		c.2307T>C	p.Tyr769Tyr	synonymous	Exon 18 of 27	NP_002411.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.2373T>C	p.Tyr791Tyr	synonymous	Exon 19 of 28	ENSP00000256552.7
	TRPM1	ENST00000558445.6	TSL:1	c.2424T>C	p.Tyr808Tyr	synonymous	Exon 18 of 27	ENSP00000452946.2
	TRPM1	ENST00000397795.7	TSL:1	c.2307T>C	p.Tyr769Tyr	synonymous	Exon 18 of 27	ENSP00000380897.2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36309 AN: 152022 Hom.: 4496 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.253

GnomAD2 exomes AF: 0.226 AC: 56427 AN: 249138 AF XY: 0.226

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.00863

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.235 AC: 343354 AN: 1461452 Hom.: 42039 Cov.: 36 AF XY: 0.233 AC XY: 169192 AN XY: 727020

African (AFR) AF: 0.263 AC: 8809 AN: 33468

American (AMR) AF: 0.269 AC: 12007 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 6131 AN: 26132

East Asian (EAS) AF: 0.0220 AC: 874 AN: 39694

South Asian (SAS) AF: 0.160 AC: 13774 AN: 86244

European-Finnish (FIN) AF: 0.259 AC: 13806 AN: 53400

Middle Eastern (MID) AF: 0.266 AC: 1534 AN: 5768

European-Non Finnish (NFE) AF: 0.246 AC: 273079 AN: 1111656

Other (OTH) AF: 0.221 AC: 13340 AN: 60382

GnomAD4 genome AF: 0.239 AC: 36361 AN: 152140 Hom.: 4502 Cov.: 33 AF XY: 0.238 AC XY: 17703 AN XY: 74376

African (AFR) AF: 0.258 AC: 10707 AN: 41500

American (AMR) AF: 0.251 AC: 3834 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5186

South Asian (SAS) AF: 0.148 AC: 713 AN: 4816

European-Finnish (FIN) AF: 0.249 AC: 2636 AN: 10570

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

European-Non Finnish (NFE) AF: 0.247 AC: 16768 AN: 67988

Other (OTH) AF: 0.253 AC: 536 AN: 2116

Alfa AF: 0.245 Hom.: 19709

Bravo AF: 0.244

Asia WGS AF: 0.0980 AC: 343 AN: 3478

EpiCase AF: 0.252

EpiControl AF: 0.259

ClinVar

ClinVar submissions as Germline

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	-0.84
CADD	Benign	0.56
DANN	Benign	0.55
PhyloP100		-0.99
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12913672; hg19: chr15-31330313;