15-31061185-A-G

Position:

• chr15-31061185-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001252024.2(TRPM1):​c.1162+257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,186 control chromosomes in the GnomAD database, including 26,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (26136 hom., cov: 32)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.492

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-31061185-A-G is Benign according to our data. Variant chr15-31061185-A-G is described in ClinVar as [Benign]. Clinvar id is 1295685.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM1	NM_001252024.2	c.1162+257T>C		intron_variant		ENST00000256552.11
TRPM1	NM_001252020.2	c.1213+257T>C		intron_variant
TRPM1	NM_002420.6	c.1096+257T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM1	ENST00000256552.11	c.1162+257T>C		intron_variant		1	NM_001252024.2	P4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84055 AN: 152068 Hom.: 26131 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.553 AC: 84089 AN: 152186 Hom.: 26136 Cov.: 32 AF XY: 0.560 AC XY: 41682 AN XY: 74414

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.585

Alfa AF: 0.638 Hom.: 41473

Bravo AF: 0.533

Asia WGS AF: 0.695 AC: 2416 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs2278133; hg19: chr15-31353388;