rs11142517

Variant names:

• chr9-70629264-C-T
• rs11142517
• NM_001366145.2:c.1633-3747G>A

Variant summary

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

The NM_001366145.2(TRPM3):​c.1633-3747G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.46 (14057 hom., cov: 16)
• Consequence: TRPM3 NM_001366145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 2 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)

ENSG00000308298 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366145.2	c.1633-3747G>A		intron_variant	Intron 12 of 25	ENST00000677713.2	NP_001353074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000677713.2	c.1633-3747G>A		intron_variant	Intron 12 of 25		NM_001366145.2	ENSP00000503830.2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 53780 AN: 115996 Hom.: 14051 Cov.: 16

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.464 AC: 53804 AN: 116070 Hom.: 14057 Cov.: 16 AF XY: 0.463 AC XY: 24777 AN XY: 53570

African (AFR) AF: 0.229 AC: 7332 AN: 31962

American (AMR) AF: 0.506 AC: 4485 AN: 8856

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1607 AN: 3082

East Asian (EAS) AF: 0.321 AC: 1022 AN: 3180

South Asian (SAS) AF: 0.522 AC: 1580 AN: 3026

European-Finnish (FIN) AF: 0.644 AC: 2967 AN: 4608

Middle Eastern (MID) AF: 0.531 AC: 103 AN: 194

European-Non Finnish (NFE) AF: 0.571 AC: 33610 AN: 58864

Other (OTH) AF: 0.495 AC: 741 AN: 1496

Alfa AF: 0.512 Hom.: 2645

Bravo AF: 0.436

Asia WGS AF: 0.428 AC: 1482 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		0.052
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11142517; hg19: chr9-73244180;