chr15-31046297-T-G

Variant names:

• chr15-31046297-T-G
• rs12907509
• NM_001252024.2:c.1765-64A>C

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.1765-64A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,492,790 control chromosomes in the GnomAD database, including 13,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1772 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12163 hom.)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.336
• Publications: 2 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 (BayesDel_noAF=-0.79).
• BP6: Variant 15-31046297-T-G is Benign according to our data. Variant chr15-31046297-T-G is described in ClinVar as Benign. ClinVar VariationId is 1252603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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.1765-64A>C		intron	N/A	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.1816-64A>C		intron	N/A	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.1699-64A>C		intron	N/A	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.1765-64A>C		intron	N/A	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.1816-64A>C		intron	N/A	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.1699-64A>C		intron	N/A	ENSP00000380897.2	Q7Z4N2-1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22246 AN: 150194 Hom.: 1767 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.129 AC: 173587 AN: 1342480 Hom.: 12163 AF XY: 0.128 AC XY: 86655 AN XY: 674554

African (AFR) AF: 0.200 AC: 5877 AN: 29376

American (AMR) AF: 0.200 AC: 8873 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 2648 AN: 25360

East Asian (EAS) AF: 0.0220 AC: 859 AN: 39028

South Asian (SAS) AF: 0.118 AC: 9901 AN: 83686

European-Finnish (FIN) AF: 0.174 AC: 9211 AN: 53036

Middle Eastern (MID) AF: 0.156 AC: 855 AN: 5464

European-Non Finnish (NFE) AF: 0.128 AC: 128562 AN: 1005682

Other (OTH) AF: 0.121 AC: 6801 AN: 56380

GnomAD4 genome AF: 0.148 AC: 22293 AN: 150310 Hom.: 1772 Cov.: 32 AF XY: 0.149 AC XY: 10952 AN XY: 73506

African (AFR) AF: 0.196 AC: 7788 AN: 39748

American (AMR) AF: 0.167 AC: 2550 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 339 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5186

South Asian (SAS) AF: 0.112 AC: 542 AN: 4818

European-Finnish (FIN) AF: 0.167 AC: 1770 AN: 10584

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8796 AN: 67990

Other (OTH) AF: 0.134 AC: 279 AN: 2084

Alfa AF: 0.0895 Hom.: 134

Bravo AF: 0.149

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

ClinVar submissions

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	3.2
DANN	Benign	0.74
PhyloP100		0.34
Mutation Taster		=100/0	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: rs12907509; hg19: chr15-31338500;