rs3809578

Positions:

• chr15-31102334-G-A
• chr15-31102334-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252020.2(TRPM1):​c.55-25350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,090 control chromosomes in the GnomAD database, including 10,992 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 0.37 (10992 hom., cov: 33)
• Consequence: TRPM1 NM_001252020.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM1	NM_001252020.2	c.55-25350C>T		intron_variant			NP_001238949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000558445.6	c.55-25350C>T		intron_variant		1		ENSP00000452946.2
TRPM1	ENST00000559177.6	c.55-25350C>T		intron_variant		5		ENSP00000453477.2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55847 AN: 151972 Hom.: 10999 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.367 AC: 55855 AN: 152090 Hom.: 10992 Cov.: 33 AF XY: 0.372 AC XY: 27675 AN XY: 74344

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.392

Alfa AF: 0.381 Hom.: 24305

Bravo AF: 0.367

Asia WGS AF: 0.536 AC: 1862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3809578; hg19: chr15-31394537;