rs4744608

Variant names:

• chr9-70666061-C-G
• rs4744608
• NM_001366145.2:c.1345+15445G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-70666061-C-G
• chr9-70666061-C-T

Variant summary

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

The NM_001366145.2(TRPM3):​c.1345+15445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,086 control chromosomes in the GnomAD database, including 11,356 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 0.38 (11356 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.1345+15445G>C		intron_variant	Intron 9 of 25	ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.1345+15445G>C		intron_variant	Intron 9 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57567 AN: 151968 Hom.: 11334 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.379 AC: 57630 AN: 152086 Hom.: 11356 Cov.: 32 AF XY: 0.376 AC XY: 27963 AN XY: 74336

African (AFR) AF: 0.474 AC: 19640 AN: 41474

American (AMR) AF: 0.345 AC: 5273 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2387 AN: 5170

South Asian (SAS) AF: 0.388 AC: 1868 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3191 AN: 10584

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22811 AN: 67972

Other (OTH) AF: 0.364 AC: 767 AN: 2110

Alfa AF: 0.351 Hom.: 1212

Bravo AF: 0.390

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.32
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4744608; hg19: chr9-73280977;