15-31077055-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001252024.2(TRPM1):c.4-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 992,454 control chromosomes in the GnomAD database, including 114,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17811 hom., cov: 33)
  • Exomes 𝑓: 0.47 (96977 hom.)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-31077055-C-T is Benign according to our data. Variant chr15-31077055-C-T is described in ClinVar as [Benign]. Clinvar id is 1233386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM1	NM_001252024.2	c.4-71G>A		intron_variant		ENST00000256552.11
TRPM1	NM_001252020.2	c.55-71G>A		intron_variant
TRPM1	NM_001252030.2	c.-63-71G>A		intron_variant
TRPM1	NM_002420.6	c.-63-71G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000256552.11	c.4-71G>A		intron_variant		1	NM_001252024.2	P4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72648 AN: 151994 Hom.: 17802 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.472 AC: 396781 AN: 840342 Hom.: 96977 AF XY: 0.468 AC XY: 206435 AN XY: 440666

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.478 AC: 72691 AN: 152112 Hom.: 17811 Cov.: 33 AF XY: 0.482 AC XY: 35836 AN XY: 74342

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.482

Alfa AF: 0.461 Hom.: 2073

Bravo AF: 0.475

Asia WGS AF: 0.556 AC: 1932 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.49

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: rs4779818; hg19: chr15-31369258; COSMIC: COSV56632243;