chr15-31001251-C-T

Position:

• chr15-31001251-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001252024.2(TRPM1):​c.*571G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,982 control chromosomes in the GnomAD database, including 24,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24004 hom., cov: 31)
  • Exomes 𝑓: 0.50 (6 hom.)
• Consequence: TRPM1 NM_001252024.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0360

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-31001251-C-T is Benign according to our data. Variant chr15-31001251-C-T is described in ClinVar as [Benign]. Clinvar id is 315480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.*571G>A		3_prime_UTR_variant	28/28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2	c.*571G>A		3_prime_UTR_variant	27/27		NP_001238949.1
TRPM1	NM_002420.6	c.*571G>A		3_prime_UTR_variant	27/27		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.*571G>A		3_prime_UTR_variant	28/28	1	NM_001252024.2	ENSP00000256552	P4
	ENST00000665655.1	n.71+9010C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83376 AN: 151820 Hom.: 23962 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.500 AC: 22 AN: 44 Hom.: 6 Cov.: 0 AF XY: 0.500 AC XY: 11 AN XY: 22

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.549 AC: 83466 AN: 151938 Hom.: 24004 Cov.: 31 AF XY: 0.542 AC XY: 40225 AN XY: 74254

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.562

Alfa AF: 0.492 Hom.: 5613

Bravo AF: 0.552

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital stationary night blindness 1C Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.22

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: rs11070718; hg19: chr15-31293454;