chr15-31132799-C-T

Variant names:

• chr15-31132799-C-T
• rs11638121
• ENST00000558445.6:c.54+28107G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558445.6(TRPM1):​c.54+28107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,088 control chromosomes in the GnomAD database, including 1,877 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 0.15 (1877 hom., cov: 32)
• Consequence: TRPM1 ENST00000558445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae)
• TRPM1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252020.2	c.54+28107G>A		intron_variant	Intron 1 of 26		NP_001238949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000558445.6	c.54+28107G>A		intron_variant	Intron 1 of 26	1		ENSP00000452946.2
TRPM1	ENST00000559177.6	c.54+28107G>A		intron_variant	Intron 1 of 7	5		ENSP00000453477.2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23130 AN: 151970 Hom.: 1881 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.152 AC: 23120 AN: 152088 Hom.: 1877 Cov.: 32 AF XY: 0.149 AC XY: 11076 AN XY: 74336

African (AFR) AF: 0.149 AC: 6181 AN: 41508

American (AMR) AF: 0.134 AC: 2050 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 626 AN: 3472

East Asian (EAS) AF: 0.00349 AC: 18 AN: 5164

South Asian (SAS) AF: 0.0750 AC: 361 AN: 4816

European-Finnish (FIN) AF: 0.179 AC: 1888 AN: 10560

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11507 AN: 67976

Other (OTH) AF: 0.165 AC: 348 AN: 2114

Alfa AF: 0.156 Hom.: 207

Bravo AF: 0.150

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.28
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11638121; hg19: chr15-31425002;