9-70692704-G-C

Variant names:

• chr9-70692704-G-C
• rs10511985
• NM_001366145.2:c.1273-11126C>G

Variant summary

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

The NM_001366145.2(TRPM3):​c.1273-11126C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,048 control chromosomes in the GnomAD database, including 10,246 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 0.36 (10246 hom., cov: 32)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 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.1273-11126C>G		intron	N/A	NP_001353074.1
	TRPM3	NM_001366147.2		c.1348-11126C>G		intron	N/A	NP_001353076.1
	TRPM3	NM_001366141.2		c.1279-11126C>G		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.1273-11126C>G		intron	N/A	ENSP00000503830.2
	TRPM3	ENST00000377110.9	TSL:1	c.1273-11126C>G		intron	N/A	ENSP00000366314.4
	TRPM3	ENST00000377111.8	TSL:1	c.1273-11126C>G		intron	N/A	ENSP00000366315.4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55054 AN: 151930 Hom.: 10227 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.362 AC: 55111 AN: 152048 Hom.: 10246 Cov.: 32 AF XY: 0.361 AC XY: 26840 AN XY: 74332

African (AFR) AF: 0.420 AC: 17423 AN: 41452

American (AMR) AF: 0.347 AC: 5307 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2386 AN: 5172

South Asian (SAS) AF: 0.388 AC: 1873 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3083 AN: 10572

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22603 AN: 67966

Other (OTH) AF: 0.352 AC: 745 AN: 2116

Alfa AF: 0.327 Hom.: 1029

Bravo AF: 0.372

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.65
PhyloP100		-0.15
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: rs10511985; hg19: chr9-73307620;