15-31001792-TAA-TAAA

Variant names:

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

Variant summary

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

The NM_001252024.2(TRPM1):​c.*29dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,129,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: TRPM1 NM_001252024.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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.*29dupT		3_prime_UTR	Exon 28 of 28	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_001252020.2		c.*29dupT		3_prime_UTR	Exon 27 of 27	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_002420.6		c.*29dupT		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.*29dupT		3_prime_UTR	Exon 28 of 28	ENSP00000256552.7	Q7Z4N2-6
	TRPM1	ENST00000558445.6	TSL:1	c.*29dupT		3_prime_UTR	Exon 27 of 27	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000397795.7	TSL:1	c.*29dupT		3_prime_UTR	Exon 27 of 27	ENSP00000380897.2	Q7Z4N2-1

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 50 AN: 149130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.000204

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000194

Gnomad OTH AF: 0.000492

GnomAD2 exomes AF: 0.0133 AC: 1633 AN: 122330 AF XY: 0.0134

Gnomad AFR exome AF: 0.00491

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0195

Gnomad EAS exome AF: 0.00743

Gnomad FIN exome AF: 0.0198

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.0112 AC: 10985 AN: 980424 Hom.: 0 Cov.: 32 AF XY: 0.0106 AC XY: 5195 AN XY: 487944

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

African (AFR) AF: 0.00894 AC: 204 AN: 22818

American (AMR) AF: 0.0119 AC: 370 AN: 31138

Ashkenazi Jewish (ASJ) AF: 0.00986 AC: 169 AN: 17144

East Asian (EAS) AF: 0.00374 AC: 104 AN: 27782

South Asian (SAS) AF: 0.00991 AC: 570 AN: 57526

European-Finnish (FIN) AF: 0.00759 AC: 254 AN: 33484

Middle Eastern (MID) AF: 0.0101 AC: 45 AN: 4446

European-Non Finnish (NFE) AF: 0.0119 AC: 8878 AN: 745492

Other (OTH) AF: 0.00963 AC: 391 AN: 40594

⚠️ 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: 0.000335 AC: 50 AN: 149206 Hom.: 0 Cov.: 32 AF XY: 0.000412 AC XY: 30 AN XY: 72732

African (AFR) AF: 0.000220 AC: 9 AN: 40930

American (AMR) AF: 0.00140 AC: 21 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.000585 AC: 3 AN: 5128

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4740

European-Finnish (FIN) AF: 0.000204 AC: 2 AN: 9794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000194 AC: 13 AN: 66982

Other (OTH) AF: 0.000487 AC: 1 AN: 2054

Alfa AF: 0.0272 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital Stationary Night Blindness, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4
Mutation Taster		=93/7	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: COSV56632926; COSMIC: COSV56632926;