15-31001792-TAA-TA

Variant names:

• chr15-31001792-TA-T
• rs563082388
• NM_001252024.2:c.*29delT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001252024.2(TRPM1):​c.*29delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,212,530 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (0 hom.)
• Consequence: TRPM1 NM_001252024.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

ENSG00000259720 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00318 (3384/1063334) while in subpopulation AMR AF= 0.00984 (317/32216). AF 95% confidence interval is 0.00895. There are 0 homozygotes in gnomad4_exome. There are 1640 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.*29delT		3_prime_UTR_variant	Exon 28 of 28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2	c.*29delT		3_prime_UTR_variant	Exon 27 of 27		NP_001238949.1
TRPM1	NM_002420.6	c.*29delT		3_prime_UTR_variant	Exon 27 of 27		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552	c.*29delT		3_prime_UTR_variant	Exon 28 of 28	1	NM_001252024.2	ENSP00000256552.7

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 93 AN: 149118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.000842

Gnomad FIN AF: 0.000716

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000269

Gnomad OTH AF: 0.000983

GnomAD4 exome AF: 0.00318 AC: 3384 AN: 1063334 Hom.: 0 Cov.: 32 AF XY: 0.00310 AC XY: 1640 AN XY: 529822

Gnomad4 AFR exome AF: 0.00680

Gnomad4 AMR exome AF: 0.00984

Gnomad4 ASJ exome AF: 0.00422

Gnomad4 EAS exome AF: 0.000737

Gnomad4 SAS exome AF: 0.00562

Gnomad4 FIN exome AF: 0.00436

Gnomad4 NFE exome AF: 0.00266

Gnomad4 OTH exome AF: 0.00302

GnomAD4 genome AF: 0.000623 AC: 93 AN: 149196 Hom.: 0 Cov.: 32 AF XY: 0.000701 AC XY: 51 AN XY: 72730

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.000267

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.000844

Gnomad4 FIN AF: 0.000716

Gnomad4 NFE AF: 0.000269

Gnomad4 OTH AF: 0.000974

Alfa AF: 0.0284 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs563082388; hg19: chr15-31293995;