15-31001792-TAA-TA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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
• Publications: 0 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

ENSG00000259720 (HGNC:58477):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.*29delT		3_prime_UTR	Exon 28 of 28	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.*29delT		3_prime_UTR	Exon 27 of 27	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.*29delT		3_prime_UTR	Exon 27 of 27	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.*29delT		3_prime_UTR	Exon 28 of 28	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.*29delT		3_prime_UTR	Exon 27 of 27	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.*29delT		3_prime_UTR	Exon 27 of 27	ENSP00000380897.2	Q7Z4N2-1

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

GnomAD2 exomes AF: 0.0128 AC: 1562 AN: 122330 AF XY: 0.0121

Gnomad AFR exome AF: 0.00590

Gnomad AMR exome AF: 0.0200

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.00795

Gnomad FIN exome AF: 0.0147

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.0157

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00680 AC: 167 AN: 24548

American (AMR) AF: 0.00984 AC: 317 AN: 32216

Ashkenazi Jewish (ASJ) AF: 0.00422 AC: 79 AN: 18706

East Asian (EAS) AF: 0.000737 AC: 22 AN: 29858

South Asian (SAS) AF: 0.00562 AC: 343 AN: 61026

European-Finnish (FIN) AF: 0.00436 AC: 154 AN: 35282

Middle Eastern (MID) AF: 0.00151 AC: 7 AN: 4650

European-Non Finnish (NFE) AF: 0.00266 AC: 2162 AN: 812980

Other (OTH) AF: 0.00302 AC: 133 AN: 44068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00137 AC: 56 AN: 40922

American (AMR) AF: 0.000267 AC: 4 AN: 14964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5130

South Asian (SAS) AF: 0.000844 AC: 4 AN: 4738

European-Finnish (FIN) AF: 0.000716 AC: 7 AN: 9778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000269 AC: 18 AN: 66982

Other (OTH) AF: 0.000974 AC: 2 AN: 2054

Alfa AF: 0.0284 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs563082388; hg19: chr15-31293995; COSMIC: COSV56638531; COSMIC: COSV56638531;