9-71301156-T-G

Variant names:

• chr9-71301156-T-G
• rs1566838
• ENST00000354500.6:n.252+145497A>C

Variant summary

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

The ENST00000354500.6(TRPM3):​n.252+145497A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,924 control chromosomes in the GnomAD database, including 17,222 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 0.47 (17222 hom., cov: 31)
• Consequence: TRPM3 ENST00000354500.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• 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)

LOC107987079 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 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+145497A>C		intron	N/A	NP_001353070.1
	TRPM3	NM_001366142.2		c.183+145497A>C		intron	N/A	NP_001353071.1
	TRPM3	NM_001366143.2		c.183+145497A>C		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+145497A>C		intron	N/A
	TRPM3	ENST00000357533.7	TSL:5	c.183+145497A>C		intron	N/A	ENSP00000350140.2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71359 AN: 151806 Hom.: 17215 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.470 AC: 71407 AN: 151924 Hom.: 17222 Cov.: 31 AF XY: 0.469 AC XY: 34833 AN XY: 74256

African (AFR) AF: 0.559 AC: 23163 AN: 41424

American (AMR) AF: 0.436 AC: 6658 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1737 AN: 3462

East Asian (EAS) AF: 0.584 AC: 3026 AN: 5178

South Asian (SAS) AF: 0.507 AC: 2440 AN: 4810

European-Finnish (FIN) AF: 0.381 AC: 4020 AN: 10556

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28748 AN: 67924

Other (OTH) AF: 0.479 AC: 1010 AN: 2110

Alfa AF: 0.440 Hom.: 12110

Bravo AF: 0.477

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0050
DANN	Benign	0.45
PhyloP100		-2.9
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: rs1566838; hg19: chr9-73916072;