rs477084

chr9-71075752-A-C

Variant summary

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

The NM_001366145.2(TRPM3):c.177+45426T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,082 control chromosomes in the GnomAD database, including 5,142 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 0.24 (5142 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM3	NM_001366145.2	c.177+45426T>G		intron_variant		ENST00000677713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM3	ENST00000677713.2	c.177+45426T>G		intron_variant			NM_001366145.2	P4

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37259 AN: 151964 Hom.: 5141 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.245 AC: 37256 AN: 152082 Hom.: 5142 Cov.: 32 AF XY: 0.247 AC XY: 18391 AN XY: 74340

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.267

Alfa AF: 0.253 Hom.: 999

Bravo AF: 0.241

Asia WGS AF: 0.322 AC: 1123 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.35
Dann	Benign	0.61

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: rs477084; hg19: chr9-73690668; COSMIC: COSV62665619;