rs4745062

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354500.6(TRPM3):​n.252+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 ENST00000354500.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 9 publications found

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]

TRPM3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cataract 50 with or without glaucoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cataract-glaucoma syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354500.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366141.2		c.183+277305G>A		intron	N/A	NP_001353070.1
	TRPM3	NM_001366142.2		c.183+277305G>A		intron	N/A	NP_001353071.1
	TRPM3	NM_001366143.2		c.183+277305G>A		intron	N/A	NP_001353072.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000354500.6	TSL:1	n.252+277305G>A		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.183+277305G>A		intron	N/A	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

African (AFR) AF: 0.330 AC: 13678 AN: 41456

American (AMR) AF: 0.456 AC: 6946 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3466

East Asian (EAS) AF: 0.518 AC: 2673 AN: 5160

South Asian (SAS) AF: 0.489 AC: 2360 AN: 4824

European-Finnish (FIN) AF: 0.499 AC: 5251 AN: 10524

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27905 AN: 67968

Other (OTH) AF: 0.403 AC: 851 AN: 2112

Alfa AF: 0.409 Hom.: 25809

Bravo AF: 0.399

Asia WGS AF: 0.519 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.56
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4745062; hg19: chr9-73784264;