NM_001252024.2:c.1765-64A>C

Variant names:

• chr15-31046297-T-G
• rs12907509
• NM_001252024.2:c.1765-64A>C

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.1765-64A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,492,790 control chromosomes in the GnomAD database, including 13,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1772 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12163 hom.)
• Consequence: TRPM1 NM_001252024.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.336

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-31046297-T-G is Benign according to our data. Variant chr15-31046297-T-G is described in ClinVar as [Benign]. Clinvar id is 1252603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM1	NM_001252024.2	c.1765-64A>C		intron_variant	Intron 15 of 27	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2	c.1816-64A>C		intron_variant	Intron 14 of 26		NP_001238949.1
TRPM1	NM_002420.6	c.1699-64A>C		intron_variant	Intron 14 of 26		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11	c.1765-64A>C		intron_variant	Intron 15 of 27	1	NM_001252024.2	ENSP00000256552.7

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22246 AN: 150194 Hom.: 1767 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.129 AC: 173587 AN: 1342480 Hom.: 12163 AF XY: 0.128 AC XY: 86655 AN XY: 674554

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.148 AC: 22293 AN: 150310 Hom.: 1772 Cov.: 32 AF XY: 0.149 AC XY: 10952 AN XY: 73506

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0977

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0895 Hom.: 134

Bravo AF: 0.149

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.74

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: rs12907509; hg19: chr15-31338500;