rs4745062

Variant names:

• chr9-71169348-C-T
• rs4745062
• ENST00000354500.6:n.252+277305G>A

Variant summary

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

The NM_001366141.2(TRPM3):​c.183+277305G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,964 control chromosomes in the GnomAD database, including 12,725 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 0.40 (12725 hom., cov: 32)
• Consequence: TRPM3 NM_001366141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

Genes affected

TRPM3 (HGNC:17992): (transient receptor potential cation channel subfamily M member 3) The product of this gene belongs to the family of transient receptor potential (TRP) channels. TRP channels are cation-selective channels important for cellular calcium signaling and homeostasis. The protein encoded by this gene mediates calcium entry, and this entry is potentiated by calcium store depletion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366141.2	c.183+277305G>A		intron_variant	Intron 1 of 24		NP_001353070.1
TRPM3	NM_001366142.2	c.183+277305G>A		intron_variant	Intron 1 of 26		NP_001353071.1
TRPM3	NM_001366143.2	c.183+277305G>A		intron_variant	Intron 1 of 25		NP_001353072.1
TRPM3	NM_001366144.2	c.183+277305G>A		intron_variant	Intron 1 of 6		NP_001353073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000354500.6	n.252+277305G>A		intron_variant	Intron 1 of 5	1
TRPM3	ENST00000357533.6	c.183+277305G>A		intron_variant	Intron 1 of 24	5		ENSP00000350140.2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61403 AN: 151846 Hom.: 12704 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.405 AC: 61471 AN: 151964 Hom.: 12725 Cov.: 32 AF XY: 0.412 AC XY: 30572 AN XY: 74250

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.403

Alfa AF: 0.413 Hom.: 15790

Bravo AF: 0.399

Asia WGS AF: 0.519 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4745062; hg19: chr9-73784264;