ENST00000558445.6:c.55-24895G>T

Variant names:

• chr15-31101879-C-A
• rs11070811
• ENST00000558445.6:c.55-24895G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000558445.6(TRPM1):​c.55-24895G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: TRPM1 ENST00000558445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 6 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558445.6. 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_001252020.2		c.55-24895G>T		intron	N/A	NP_001238949.1	Q7Z4N2-5
	TRPM1	NM_001252024.2	MANE Select	c.-306G>T		upstream_gene	N/A	NP_001238953.1	Q7Z4N2-6
	TRPM1	NM_002420.6		c.-286G>T		upstream_gene	N/A	NP_002411.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM1	ENST00000558445.6	TSL:1	c.55-24895G>T		intron	N/A	ENSP00000452946.2	Q7Z4N2-5
	TRPM1	ENST00000559177.6	TSL:5	c.55-24895G>T		intron	N/A	ENSP00000453477.2	H0YM61
	TRPM1	ENST00000256552.11	TSL:1 MANE Select	c.-306G>T		upstream_gene	N/A	ENSP00000256552.7	Q7Z4N2-6

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		0.64
PromoterAI		0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11070811; hg19: chr15-31394082;