rs1011308

Variant names:

• chr9-70673340-A-G
• rs1011308
• NM_001366145.2:c.1345+8166T>C

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+8166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,918 control chromosomes in the GnomAD database, including 6,450 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 0.29 (6450 hom., cov: 30)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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)

LOC105376078 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366145.2. 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_001366145.2	MANE Select	c.1345+8166T>C		intron	N/A	NP_001353074.1
	TRPM3	NM_001366147.2		c.1420+8166T>C		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.1351+8166T>C		intron	N/A	NP_001353070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000677713.2	MANE Select	c.1345+8166T>C		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.1345+8166T>C		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.1345+8166T>C		intron	N/A	ENSP00000366315.4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43430 AN: 151800 Hom.: 6449 Cov.: 30

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.286 AC: 43449 AN: 151918 Hom.: 6450 Cov.: 30 AF XY: 0.289 AC XY: 21461 AN XY: 74252

African (AFR) AF: 0.317 AC: 13135 AN: 41412

American (AMR) AF: 0.222 AC: 3390 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3466

East Asian (EAS) AF: 0.183 AC: 944 AN: 5156

South Asian (SAS) AF: 0.334 AC: 1603 AN: 4798

European-Finnish (FIN) AF: 0.346 AC: 3655 AN: 10552

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18936 AN: 67954

Other (OTH) AF: 0.278 AC: 587 AN: 2112

Alfa AF: 0.275 Hom.: 17136

Bravo AF: 0.271

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.47
PhyloP100		-1.0
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: rs1011308; hg19: chr9-73288256;