15-31030659-T-C

Position:

• chr15-31030659-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252024.2(TRPM1):​c.3127+324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,008 control chromosomes in the GnomAD database, including 15,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (15008 hom., cov: 32)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.3127+324A>G		intron_variant		ENST00000256552.11	NP_001238953.1
LOC105370752	XR_932055.2	n.278+3548T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.3127+324A>G		intron_variant		1	NM_001252024.2	ENSP00000256552	P4
	ENST00000665655.1	n.218+3548T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60189 AN: 151890 Hom.: 14960 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60297 AN: 152008 Hom.: 15008 Cov.: 32 AF XY: 0.385 AC XY: 28591 AN XY: 74322

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.384

Alfa AF: 0.337 Hom.: 2803

Bravo AF: 0.419

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs2042613; hg19: chr15-31322862;